Institute for Molecular Animal Breeding and Biotechnology

Institute of Molecular Animal Breeding
and Biotechnology

..............Prof. Dr. Eckhard Wolf, Genzentrum der LMU-München

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	Molecular Mechanisms of Mammalian Growth Regulation
	Biology and Biotechnology of Reproduction
	Mouse Genetics and ENU-Mutagenesis
	Mammalian Transgenic Technology

Mammalian Transgenic Technology

Transgenic technology in farm animals species has a plethora of potential applications, including the modification of production traits, the production of therapeutic proteins (gene farming), the genetic modification of pigs for xenotransplantation, and the production of new animal models for scientific questions which cannot be properly addressed in the classical rodent models. Although the production of transgenic farm animals by pronuclear DNA-microinjection has been established in 1985 and is successfully used in our lab, this technique being relatively inefficient causes high costs. Thus, we are working on alternative routes of transgenesis in livestock species. Based on our long-standing experience in bovine cloning, we established efficient protocols for nuclear transfer using transfected cells and produced transgenic cattle. The same technique is now used for gene targeting experiments. Recently, we established a highly efficient technique of transgenesis in farm animals which is based on the use of lentiviral vectors. This was achieved in close collaboration with the group of Prof. Alexander Pfeifer, Department of Pharmacy, University of Munich. This technique is being used for the rapid and cost efficient evaluation of novel transgenes (high performance multitransgenics) in various fields, including xenotransplantation, prion research, and metabolic disorders.

Selected original papers

Zakhartchenko V, Mueller S, Alberio R, Schernthaner W, Stojkovic M, Wenigerkind H, Wanke R, Lassnig C, Mueller M, Wolf E, Brem G (2001) Nuclear transfer in cattle with non-transfected and transfected fetal or cloned transgenic fetal and postnatal fibroblasts. Mol Reprod Dev 60, 362 369

Hofmann A, Kessler B, Ewerling S, Weppert M, Vogg B, Ludwig H, Stojkovic M, Boelhauve M, Brem G, Wolf E, Pfeifer A (2003) Efficient transgenesis in farm animals by lentiviral vectors. EMBO Rep 4, 1054-1058

Selected review articles

Wolf E, Schernthaner W, Zakhartchenko V, Prelle K, Stojkovic M, Brem G (2000) Transgenic technology in farm animals - progress and perspectives. Exp Physiol 85, 615-625

Mouse Genetics and ENU-Mutagenesis

Animal models are essential to understand the genetics and pathogenesis of human diseases. The mouse is intensively used as a model system due to the similarity of genome organization, developmental and biochemical pathways and physiology. Mouse models can be established in a genotype- and a phenotype-driven way. A broad spectrum of transgenic (incl. pronuclear microinjection of BACs), knock-out and knock-in techniques is established in our lab and employed for our own projects and in collaboration with partners from different disciplines. In addition our lab contributes to a large enterprise aiming at the phenotype-driven generation of mouse models for human diseases: the Munich ENU Mouse Mutagenesis Screen. In this consortium we are part of the core facility and identify clinically relevant mouse models by measuring clinical-chemical and hematological parameters. With this expertise, we are also part of the recently established German Mouse Clinic (GMC), a multidisciplinary center for systematic phenotyping of mouse mutants.

Selected original papers

Hrabé de Angelis M, Flaswinkel H, Fuchs H, Rathkolb B, Soewarto D, Marschall S, Heffner S, Pargent W, Wuensch K, Jung M, Reis A, Richter T, Alessandrini F, Jakob T, Fuchs E, Kolb H, Kremmer E, Schaeble K, Rollinski B, Roscher A, Peters C, Meitinger T, Strom T, Steckler T, Holsboer F, Klopstock T, Gekeler F, Schindewolf C, Jung T, Avraham K, Behrendt H, Ring J, Zimmer A, Schughart K, Pfeffer K, Wolf E, Balling R (2000) Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat Genet 25, 444-447

Rathkolb B, Decker T, Fuchs E, Soewarto D, Fella C, Heffner S, Pargent W, Wanke R, Balling R, Hrabé de Angelis M, Kolb HJ, Wolf E (2000) The clinical-chemical screen in the Munich ENU Mouse Mutagenesis Project: screening for clinically relevant phenotypes. Mamm Genome 11, 543-546

Graw J, Löster J, Soewarto D, Fuchs H, Reis A, Wolf E, Balling R, Hrabé de Angelis M (2001) Aey2, a new mutation in the beta-B2-crystallin-encoding gene of the mouse. Invest Ophthalmol Vis Sci 42, 1574-1580

Graw J, Loster J, Soewarto D, Fuchs H, Reis A, Wolf E, Balling R, Hrabé de Angelis M (2002) V76D mutation in a conserved gamma-D-crystallin region leads to dominant cataracts in mice. Mamm Genome 13, 452-455

Dunant P, Larochelle N, Thirion C, Stucka R, Ursu D, Petrof BJ, Wolf E, Lochmüller H (2003) Expression of dystrophin driven by the 1.35 kb MCK promoter ameliorates muscular dystrophy in fast, but not in slow muscles of transgenic mdx mice. Mol Ther 8, 80-89

Krebs O, Schreiner CM, Scott WJ Jr, Bell SM, Robbins DJ, Goetz JA, Alt H, Hawes N, Wolf E, Favor J (2003) Replicated anterior zeugopod (raz): a polydactylous mouse mutant with lowered Shh signaling in the limb bud. Development 130, 6037-6047

Selected review articles

Rathkolb B, Krebs O, Balling R, Hrabé de Angelis M, Wolf E (1999) Discovery and functional characterization of new genes by large scale ENU mutagenesis in mice. Arch Tierz, Dummerstorf 42, 74-85

Rathkolb B, Fuchs E, Kolb HJ, Renner-Müller I, Krebs O, Balling R, Hrabé de Angelis M, Wolf E (2000) Large-scale N-ethyl-N-nitrosourea mutagenesis of mice - from phenotypes to genes. Exp Physiol 85.6, 635-644

Biology and Biotechnology of Reproduction

Reproductive performance is one of the most important economic traits in farm animals. However, improvement of reproductive performance has been difficult due to the low heritability of this complex trait. Thus, a focus of our lab is on the understanding of important processes in biology of reproduction such as early embryo-maternal communication which is a prerequisite to establish and maintain pregnancy. Using bovine as a model system, we analyze the cross-talk between pre-implantation embryos and their maternal environment by using state-of-the-art transcriptomics and proteomics technologies (see DFG Research Unit 478/1: Mechanisms of embryo-maternal communication; www.ematko.de). Results of this project will lead to the definition of new parameters for the improvement of reproductive performance by genetic selection. Further, understanding the specific requirements of early embryos should improve the efficacy of reproductive biotechnologies, such as the in vitro production of embryos and the generation of embryos by somatic cell nuclear transfer. The latter technique is used as a model to understand basic mechanisms of nuclear reprogramming, to define the roles of epigenetic mechanisms during this process, and to experimentally evaluate maternal cytoplasmic effects on the phenotype of resulting embryos, fetuses and offspring.

Selected original papers

Bauersachs S, Blum H, Mallok S, Wenigerkind H, Rief S, Prelle K, Wolf E (2003) Regulation of ipsilateral and contralateral bovine oviduct epithelial cell function in the post-ovulation period - a transcriptomics approach. Biol Reprod 68, 1170-1177

Hiendleder S, Zakhartchenko V, Wenigerkind H, Reichenbach H-D, Brüggerhoff K, Prelle K, Brem G, Stojkovic M, Wolf E (2003) Heteroplasmy in bovine fetuses produced by intra- and intersubspecific somatic cell nuclear transfer: neutral segregation of nuclear donor mitochondrial DNA in various tissues and evidence for recipient cow mitochondria in fetal blood. Biol Reprod 68, 159-166

Santos F, Zakhartchenko V, Stojkovic M, Peters A, Jenuwein T, Wolf E, Reik W, Dean W (2003) Epigenetic marking correlates with developmental potential in cloned bovine preimplantation embryos. Curr Biol 13, 1116-1121

Shi W, Hoeflich A, Flaswinkel H, Stojkovic M, Wolf E, Zakhartchenko V (2003) Induction of a senescent-like phenotype does not confer the ability of bovine immortal cells to support the development of nuclear transfer embryos. Biol Reprod 69, 301-309

Stojkovic M, Krebs O, Kölle S, Prelle K, Assmann V, Zakhartchenko V, Sinowatz F, Wolf E (2003) Developmental regulation of hyaluronan-binding protein (RHAMM/ IHABP) expression in early bovine embryos. Biol Reprod 68, 60-66

Bauersachs S, Rehfeld S, Ulbrich S, Mallok S, Prelle K, Wenigerkind H, Einspanier R, Blum H, Wolf E (2004) Monitoring gene expression changes in bovine oviduct epithelial cells during the oestrous cycle. J Mol Endocrinol (accepted)

Hiendleder S, Prelle K, Brüggerhoff K, Reichenbach H-D, Wenigerkind H, Bebbere D, Stojkovic M, Müller S, Brem G, Zakhartchenko V, Wolf E (2004) Nuclear-cytoplasmic interactions affect in utero developmental capacity, phenotype and cellular metabolism of bovine nuclear transfer fetuses. Biol Reprod (in press)

Selected review articles

Prelle K, Zink N, Wolf E (2002) Pluripotent stem cells - model of embryonic development, tool for gene targeting, and basis of cell therapy. Anat Histol Embryol 31, 169-186

Hiendleder S, Wolf E (2003) The mitochondrial genome in embryo technologies. Reprod Dom Anim 38, 290-304

Shi, W, Zakhartchenko V, Wolf E (2003) Mammalian nuclear transfer and epigenetic reprogramming. Differentiation 71, 91-113

Wolf E, Arnold GJ, Bauersachs S, Beier HM, Blum H, Einspanier R, Fröhlich T, Herrler A, Hiendleder S, Kölle S, Prelle K, Reichenbach H-D, Stojkovic M, Wenigerkind H, Sinowatz F (2003) Embryo-maternal communication in bovine - strategies for deciphering a complex cross-talk. Reprod Dom Anim 38, 276-289

Molecular mechanisms of mammalian growth regulation

The size of an animal, organ, or appendage depends on the number and volume of the cells it contains as well as on the amount of extracellular matrix and fluid. Both local and systemic controls determine organ size, but their relative importance can vary greatly. Growth hormone and insulin-like growth factors (IGFs) are important stimulators of cell growth (cell mass increase), survival and proliferation, depending on tissue type and physiological/pathological status. These effects of IGFs are mostly transmitted through the type 1 IGF-receptor (IGF-IR). High affinity IGF-binding proteins (IGFBP-1 to -6) are capable of modulating IGF effects via different mechanisms, however their role in regulating cell size, survival and proliferation in vivo is largely unclear. Thus a focus of our lab is to functionally dissect the roles of individual components of the GH/IGF system by using transgenic and knockout mice as well as specific cellular model systems. In addition, mouse models produced by long-term divergent selection for growth parameters are used to evaluate which components of the GH/IGF-system contribute to altered growth induced by phenotypic selection.

More Details

Selected original papers

Hoeflich A, Nedbal S, Blum WF, Erhard M, Lahm H, Brem G, Kolb HJ, Wanke R, Wolf E (2001) Growth inhibition in giant growth hormone transgenic mice by overexpression of insulin-like growth factor-binding protein-2. Endocrinology 142, 1889-1898

Hoeflich A, Weber MM, Fisch T, Nedbal S, Fottner C, Elmlinger MW, Wanke R, Wolf E (2002) Insulin-like growth factor binding protein 2 (IGFBP-2) separates hypertrophic and hyperplastic effects of growth hormone (GH)/IGF-I excess on adrenocortical cells in vivo. FASEB J 16, 1721-1731

Diehl D, Hoeflich A, Wolf E, Lahm H (2004) Insulin-like growth factor-binding protein-4 inhibits colony formation of colorectal cancer cells by IGF-independent mechanisms. Cancer Res (accepted)

Hoeflich A, Bunger L, Nedbal S, Renne U, Elmlinger MW, Blum WF, Bruley C, Kolb HJ, Wolf E (2004) Growth selection in mice reveals conserved and redundant expression patterns of the insulin-like growth factor system. Gen Comp Endocrinol (accepted)

Zhou R, Flaswinkel H, Schneider MR, Lahm H, Hoeflich A, Wanke R, Wolf E (2004) Insulin-like growth factor-binding protein-4 inhibits growth of the thymus in transgenic mice. J Mol Endocrinol (accepted)

Selected review articles

Schneider MR, Lahm H, Wu M, Hoeflich A, Wolf E (2000) Transgenic mouse models for studying the functions of insulin-like growth factor-binding proteins. FASEB J 14, 629-640

Hoeflich A, Reisinger R, Lahm H, Kiess W, Blum WF, Kolb HJ, Weber MM, Wolf E (2001) Insulin-like growth factor-binding protein 2 (IGFBP-2) in tumorigenesis - protector or promoter? Cancer Res 61, 8601-8610

Schneider MR, Wolf E, Hoeflich A, Lahm H (2002) Insulin-like growth factor-binding protein-5: flexible player in the IGF system and effector on its own. J Endocrinol 172, 423-440

Zhou R, Diehl D, Hoeflich A, Lahm H, Wolf E (2003) IGF-binding protein-4: biochemical characteristics and functional consequences. J Endocrinol 178, 177-193

Molecular mechanisms of mammalian growth regulation

1.	Wolf E, Brem G (1989) A comparison of different immunoradiometric assays for detecting hGH in the serum of MT-hGH transgenic mice and controls. Acta Endocrinol (Copenh) 120 [Suppl 1], 143-144


2.	Brem G, Wanke R, Wolf E, Buchmüller T, Müller M, Brenig B, Hermanns W (1989) Multiple consequences of human growth hormone expression in transgenic mice. Mol Biol Med 6, 531-547


3.	Wanke R, Hermanns W, Folger S, Wolf E, Brem G (1991) Accelerated growth and visceral lesions in transgenic mice expressing foreign genes of the growth hormone family. An overview. Pediatr Nephrol 5, 513-521

4.	Wolf E, Rapp K, Brem G (1991) Expression of metallothionein-human growth hormone fusion genes in transgenic mice results in disproportionate skeletal gigantism. Growth Develop Aging 55, 117-127

5.	Wolf E, Brem G (1991) High dose hook-effect as a pitfall in quantifying transgene expression in metallothionein-human growth hormone (MT-hGH) transgenic mice. Clin Chem 37, 763-765

6.	Wolf E, Wanke R, Hermanns W, Brem G, Pirchner F, v Butler-Wemken I (1991) Growth characteristics of metallothionein-human growth hormone transgenic mice as compared to mice selected for high eight-week body weight and unselected controls. I. Body weight gain and external body dimensions. Growth Develop Aging 55, 225-235

7.	Wolf E, Rapp K, Wanke R, Hermanns W, Pirchner F, v Butler-Wemken I, Brem G (1991) Growth characteristics of metallothionein-human growth hormone transgenic mice as compared to mice selected for high eight-week body weight and unselected controls. II. Skeleton. Growth Develop Aging 55, 237-248


8.	Wanke R, Wolf E, Hermanns W, Folger S, Buchmüller T, Brem G (1992) The GH-transgenic mouse as an experimental model for growth research: clinical and pathological studies. Horm Res 37 [Suppl. 3], 74-87

9.	Wolf E, Kahnt E, Ehrlein J, Hermanns W, Brem G, Wanke R (1993) Effects of long-term elevated serum levels of growth hormone on life expectancy of mice: lessons from transgenic animal models. Mech Ageing Develop 68, 71-87

10.	Brem G, Hartl P, Besenfelder U, Wolf E, Zinovieva N, Pfaller R (1994) Expression of synthetic cDNA sequences encoding human insulin-like growth factor-1 (IGF-1) and its analogue [Gln58] IGF-1 in the mammary glands of transgenic rabbits. Gene 149, 351-355

11.	Wolf E, Kramer R, Blum WF, Föll J, Brem G (1994) Consequences of postnatally elevated insulin-like growth factor-II in transgenic mice: endocrine changes and effects on body and organ growth. Endocrinology 135, 1877-1886


12.	Hoeflich A, Wolf E, Braulke T, Koepf G, Kessler U, Brem G, Rascher W, Blum W, Kiess W (1995) Does the overexpression of pro-insulin-like growth factor-II in transfected human embryonic kidney fibroblasts increase the secretion of lysosomal enzymes? Eur J Biochem 232, 172-178


13.	Wolf E, Wanke R, Schenck E, Hermanns W, Brem G (1995) Effects of growth hormone overproduction on grip strength of transgenic mice. Eur J Endocrinol 133, 735 740


14.	Wolf E, Rapp K, Blum WF, Kolb H, Brem G (1995) Skeletal growth of transgenic mice with elevated levels of circulating insulin-like growth factor-II. Growth Reg 5, 177-184

15.	Wanke R, Wolf E, Brem G, Hermanns W (1996) Physiology and pathology of growth - studies in GH transgenic mice. J Anim Breed Genet 113, 445-456


16.	Wolf E, Wanke R (1996) Growth hormone overproduction in transgenic mice: phenotypic alterations and deduced animal models. In: van Zutphen, L.F.M., van der Meer, M. (eds.): Welfare of Transgenic Animals. Heidelberg: Springer-Verlag, pp 26-47

17.	Blackburn A, Schmitt A, Schmidt P, Wanke R, Hermanns W, Brem G, Wolf E (1997) Actions and interactions of growth hormone and insulin-like growth factor-II: body and organ growth of transgenic mice. Transgenic Res 6, 213-222

18.	Blackburn A, Dressendörfer RA, Blum WF, Erhard M, Brem G, Strasburger CJ, Wolf E (1997) Interactions of insulin-like growth factor-II (IGF-II) and growth hormone (GH) in vivo: circulating levels of IGF-I and IGF-binding proteins in transgenic mice. Eur J Endocrinol 137, 701-708


19.	Wolf E, Jehle, PM, Weber MM, Sauerwein H, Daxenberger A, Breier BH, Besenfelder U, Frenyo L, Brem G (1997) Human insulin-like growth factor-I produced in the mammary glands of transgenic rabbits: yield, receptor binding, mitogenic activity, and effects on IGF-binding proteins. Endocrinology 138, 307-313


20.	Dirsch VM, Wolf E, Wanke R, Schulz R, Hermanns W, Vollmar AM (1998) Effect of chronic GH overproduction on cardiac ANP expression and circulating ANP levels. Mol Cell Endocrinol 144, 109-118


21.	Hoeflich A, Schmidt P, Föll J, Rottmann O, Weber MM, Kolb HJ, Pirchner F, Wolf E (1997) Altered growth of mice divergently selected for body weight is associated with complex changes in the growth hormone/insulin-like growth factor system. Growth Horm IGF Res 8, 113-123

22.	Hoeflich A, Lahm H, Blum W, Kolb H, Wolf E (1998) Insulin-like growth factor-binding protein-2 inhibits proliferation of human embryonic kidney fibroblasts and of IGF-responsive colon carcinoma cell lines. FEBS Lett 434, 329-334

23.	Ogiolda L, Wanke R, Rottmann O, Hermanns W, Wolf E (1998) Intestinal dimensions of mice divergently selected for body weight. Anat Rec 250, 292-299


24.	Wolf E, Lahm H, Hoeflich A (1998) What is the function of IGF-II in postnatal life? Answers from transgenic mouse models. Growth Horm IGF Res 8, 185-193


25.	Zinovieva N, Lassnig C, Schams D, Besenfelder U, Wolf E, Müller S, Frenyo J, Seregi J, Müller M, Brem G (1998) Stable production of human insulin-like growth factor 1 (IGF-1) in the milk of hemi- and homozygous transgenic rabbits over several generations. Transgenic Res 7, 437-447


26.	Graichen H, Lochmüller E-M, Wolf E, Langkabel R, Stammberger T, Haubner M, Renner-Müller I, Englmeier K-H, Eckstein F (1999) A technique for 3D microstructural phenotypic characterisation of the skeletal system - preliminary data in growth hormone transgenic animals and normal controls. Anat Embryol 199, 239-248


27.	Hoeflich A, Wu M, Mohan S, Föll J, Wanke R, Froehlich T, Arnold GJ, Lahm H, Kolb HJ, Wolf E (1999) Overexpression of insulin-like growth factor-binding protein-2 reduces postnatal body weight gain in transgenic mice. Endocrinology 140, 5488-5496

28.	Jehle PM, Fussgänger RD, Blum WF, Angelus NKO, Höflich A, Wolf E, Jungwirth RJ (1999) Differential autocrine regulation of intestine epithelial cell proliferation and differentiation by insulin-like growth factor (IGF) system components. Horm Metab Res 31, 97-102

29.	Kiess W, Paquette J, Koepf G, Wolf E, Deal C (1999) Proinsulin-like growth factor-II overexpression does not alter monoallelic H19 gene expression in transfected human embryonic kidney fibroblasts. Biochem Biophys Res Commun 255, 226-230

30.	Lahm H, Allenbacher A, Höflich A, Fischer JR, Botzler C, Multhoff G, Wolf E, Sordat B (1999) Differential growth factor responsiveness and receptor expression in primary and metastatic human colorectal carcinoma cells. Contrib Oncol 54, 317-323

31.	Lochmüller E-M, Weusten A, Wolf E, Cindik E, Renner-Müller I, Eikmeier T, Eckstein F (1999) Geschlechtsspezifische Analyse der Knochenmasse normaler und Wachstumshormon-transgener Mäuse mittels Zweienergie-Röntgen-Absorptiometrie (DXA). Ann Anat 181, 191-198

32.	Wanke R, Milz S, Rieger N, Ogiolda L, Renner-Müller I, Brem G, Hermanns W, Wolf E (1999) Overgrowth of the skin in growth hormone transgenic mice depends on the presence of male gonads. J Invest Dermatol 113, 967-971

33.	Weber MM, Fottner C, Schmidt P, Brodowski KMH, Gittner K, Lahm H, Engelhardt D, Wolf E (1999) Postnatal overexpression of IGF-II in transgenic mice is associated with adrenocortical hyperplasia and enhanced steroidogenesis. Endocrinology 140, 1537-1543

34.	Weusten A, Lochmüller E-M, Cindik E, Renner-Müller I, Tysarczyk-Niemeyer G, Wolf E, Eckstein F (1999) Femoral bone mass, size and density in male and female growth hormone transgenic mice. Transgenics 3, 43-50

35.	Cindrik E, Willnecker J, Wolf E, Eckstein F (2000) Analyse femoraler Knockeneigenschaften im MT-bGH-transgenen Mausmodell mit der hochauflösenden pQCT. Osteologie 9, 85-93

36.	Hoeflich A, Fettscher O, Lahm H, Blum WF, Kolb HJ, Engelhardt D, Wolf E, Weber MM (2000) Overexpression of insulin-like growth factor-binding protein-2 results in increased tumorigenic potential in Y-1 adrenocortical tumor cells. Cancer Res 60, 834-838

37.	Lahm H, Hoeflich A, André S, Sordat B, Kaltner H, Wolf E, Gabius H-J (2000) Gene expression of galectin-9/ecalectin, a potent eosinophil chemoattractant, and/or the insertional isoform in human colorectal carcinoma cell lines and detection of frame-shift mutations for protein sequence truncations in the second functional lectin domain. Int J Oncol 17, 519-524


38.	Nedbal S, Zink N, Lahm H, Hoeflich A, Wolf E (2000) Functional dissection of the insulin-like growth factor (IGF) system - prospects for animal breeding. Arch Tierz, Dummerstorf 43, 11-18

39.	Prelle K, Wobus AM, Krebs O, Blum WF, Wolf E (2000) Overexpression of insulin-like growth factor-II in mouse embryonic stem cells promotes myogenic differentiation. Biochem Biophys Res Commun 277, 631-638


40.	Reichart U, Kappler R, Scherthan H, Wolf E, Müller M, Brem G, Aigner B (2000) Partial leptin receptor gene deletion in transgenic mice prevents expression of the membrane-bound isoforms except for Ob-Rc. Biochem Biophys Res Commun 269, 496-501

41.	Reichart U, Renner-Müller I, Höflich A, Müller OJ, Franz WM, Wolf E, Müller M, Brem G, Aigner B (2000) Contrasting obesity phenotypes uncovered by partial leptin receptor gene deletion in transgenic mice. Biochem Biophys Res Commun 269, 502-507


42.	Schneider MR, Hoeflich A, Fischer JR, Wolf E, Sordat B, Lahm H (2000) Interleukin-6 stimulates clonogenic growth of primary and metastatic human colon carcinoma cells. Cancer Lett 151, 31-38

43.	Schneider MR, Lahm H, Wu M, Hoeflich A, Wolf E (2000) Transgenic mouse models for studying the functions of insulin-like growth factor-binding proteins. FASEB J 14, 629-640

44.	Weber MM, Fottner C, Wolf E (2000) The role of the insulin-like growth factor system in adrenocortical tumourigenesis. Eur J Clin Invest 30 Suppl 3, 69-75

45.	Wolf E, Lahm H, Wu M, Wanke R, Hoeflich A (2000) Effects of IGFBP-2 overexpression in vitro and in vivo. Pediatr Nephrol 14, 572-578

46.	Brockmann GA, Haley CS, Wolf E, Karle S, Kratzsch J, Renne U, Schwerin M, Hoeflich A (2001) Genome-wide search for loci controlling serum IGF-binding protein levels of mice. FASEB J 15, 978-987

47.	Hoeflich A, Nedbal S, Blum WF, Erhard M, Lahm H, Brem G, Kolb HJ, Wanke R, Wolf E (2001) Growth inhibition in giant growth hormone transgenic mice by overexpression of insulin-like growth factor-binding protein-2. Endocrinology 142, 1889-1898

48.	Hoeflich A, Reisinger R, Lahm H, Kiess W, Blum WF, Kolb HJ, Weber MM, Wolf E (2001) Insulin-like growth factor-binding protein 2 (IGFBP-2) in tumorigenesis - protector or promoter? Cancer Res 61, 8601-8610

49.	Lahm H, André S, Hoeflich A, Fischer JR, Sordat B, Kaltner H, Wolf E, Gabius H-J (2001) Comprehensive galectin fingerprinting in a panel of 61 human tumor cell lines by RT-PCR and its implication for diagnostic and therapeutic procedures. J Cancer Res Clin Oncol 127, 375-386

50.	Lochmüller E-M, Jung V, Weusten A, Wehr U, Wolf E, Eckstein F (2001) Precision of high-resolution dual energy X-ray absorptiometry measurements of bone mineral status and body composition in small animal models. European Cells and Materials 1, 43-51

51.	Schneider MR, Zhou R, Hoeflich A, Krebs O, Schmidt J, Mohan S, Wolf E, Lahm H (2001) Insulin-like growth factor-binding protein-5 inhibits growth and induces differentiation of mouse osteosarcoma cells. Biochem Biophys Res Commun 288, 435-442

52.	Eckstein F, Lochmüller EM, Koller B, Wehr U, Weusten A, Rambeck W, Hoeflich A, Wolf E (2002) Body composition, bone mass and microstructural analysis in GH-transgenic mice reveals that skeletal changes are specific to bone compartment and gender. Growth Horm IGF Res 12, 116-125

53.	Eckstein F, Pavicic T, Nedbal S, Schmidt C, Wehr U, Rambeck W, Wolf E, Hoeflich A (2002) Insulin-like growth factor binding protein-2 (IGFBP-2) overexpression negatively regulates bone size and mass, but not density, in the absence and presence of growth hormone/IGF-I excess in transgenic mice. Anat Embryol 206, 139-148


54.	Hoeflich A, Reisinger R, Vargas GA, Elmlinger MW, Schuett B, Jehle PM, Renner-Müller I, Lahm H, Russo VC, Wolf E (2002) Mutation of the RGD sequence does not affect plasma membrane association and growth inhibitory effects of elevated IGFBP-2 in vivo. FEBS Lett 523, 63-67

55.	Hoeflich A, Weber MM, Fisch T, Nedbal S, Fottner C, Elmlinger MW, Wanke R, Wolf E (2002) Insulin-like growth factor binding protein 2 (IGFBP-2) separates hypertrophic and hyperplastic effects of growth hormone (GH)/IGF-I excess on adrenocortical cells in vivo. FASEB J 16, 1721-1731

56.	Lahm H, Gittner K, Krebs O, Sprague L, Deml E, Oesterle D, Hoeflich A, Wanke R, Wolf E (2002) Diethylnitrosamine induces long-lasting re-expression of insulin-like growth factor II during early stages of liver carcinogenesis in mice. Growth Horm IGF Res 12, 69-79

57.	Lahm H, Anrdré S, Hoeflich A, Fischer JR, Sordat B, Kaltner H, Wolf E, Gabius H-J (2003) Molecular biological fingerprinting of human lectin expression by RT-PCR. Methods Enzymol 362, 287-297

58.	Schneider MR, Wolf E, Hoeflich A, Lahm H (2002) Insulin-like growth factor-binding protein-5: flexible player in the IGF system and effector on its own. J Endocrinol 172, 423-440

59.	Zhou R, Diehl D, Hoeflich A, Lahm H, Wolf E (2003) IGF-binding protein-4: biochemical characteristics and functional consequences. J Endocrinol 178, 177-193

60.	Diehl D, Hoeflich A, Wolf E, Lahm H (2004) Insulin-like growth factor-binding protein-4 inhibits colony formation of colorectal cancer cells by IGF-independent mechanisms. Cancer Res (accepted)

61.	Hoeflich A, Fettscher O, Preta G, Lahm H, Kolb HJ, Wolf E, Weber MM (2004) Increased activity of catalase in tumor cells overexpressing IGFBP-2. Horm Metab Res (in press)

62.	Hoeflich A, Bunger L, Nedbal S, Renne U, Elmlinger MW, Blum WF, Bruley C, Kolb HJ, Wolf E (2004) Growth selection in mice reveals conserved and redundant expression patterns of the insulin-like growth factor system. Gen Comp Endocrinol (accepted)

63.	Eckstein F, Weusten A, Schmidt C, Wehr U, Wanke R, Rambeck W, Wolf E, Mohan S (2004) Longitudinal in vivo effects of growth hormone overexpression on bone in transgenic mice. J Bone Miner Res (accepted)

64.	Zhou R, Flaswinkel H, Schneider MR, Lahm H, Hoeflich A, Wanke R, Wolf E (2004) Insulin-like growth factor-binding protein-4 inhibits growth of the thymus in transgenic mice. J Mol Endocrinol (accepted)


	Back to the publications main page

Möglichkeiten der genetischen Modifikation von Schweinen für die Xenotransplantation (Bayerisches Ärzteblatt 6/2001)

Embryo-maternale Kommunikation - Strategien zur Entschlüsselung eines komplexen Dialogs (Einsichten 2/2003)

Nutztiere - quo vadite? Neue Wege durch funktionale Genomanalyse

Erzeugung von PrPC-defizienten Rindern und Rinderklonen für die BSE-Forschung (Nova Acta Leopoldina 2002)

Mammalian Transgenic Technology

1.	Masu Y, Wolf E, Holtmann B, Sendtner M, Brem G, Thoenen H (1993) Disruption of the CNTF gene results in motor neuron degeneration. Nature 365, 27-32


2.	Wolf E, Kramer R, Polejaewa I, Thoenen H, Brem G (1994) Efficient generation of chimaeric mice using embryonic stem cells after long-term culture in the presence of ciliary neurotrophic factor. Transgenic Res 3, 152-158


3.	Korte M, Carroll P, Wolf E, Brem G, Thoenen H, Bonhoeffer T (1995) Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci USA 92, 8856-8860


4.	Airaksinen MS, Koltzenburg M, Lewin GR, Masu Y, Helbig C, Wolf E, Brem G, Toyka KV, Thoenen H, Meyer M (1996) Specific sub-types of cutaneous mechanoreceptors require neurotrophin-3 following peripheral target innervation. Neuron 16, 287-295

5.	Förster R, Mattis AE, Kremmer E, Wolf E, Brem G, Lipp M (1996) A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and to specific anatomic compartments of the spleen. Cell 87, 1037-1047


6.	Peters M, Jacobs S, Ehlers M, Vollmer P, Müllberg J, Wolf E, Brem G, Meyer zum Büschenfelde K-H, Rose-John S (1996) The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6. J Exp Med 183, 1399-1406


7.	Sendtner M, Götz R, Holtmann B, Escary J-L, Masu Y, Carroll P, Wolf E, Brem G, Brulet P, Thoenen H (1996) Cryptic physiological trophic support of motoneurons by LIF revealed by double gene targeting of CNTF and LIF. Curr Biol 6, 686-694



8.	Wolf E, Kramer R, Thoenen H, Brem G (1996) Alternative culture systems for mouse embryonic stem cells. In: Arnold W, Köpf-Maier P, Micheel B (eds.): Immunodeficient Animals: Models for Cancer Research. Basel: Karger, Contrib Oncol 51, pp 214-218


9.	Wolf E (1997) Transgenic animals: an alternative? Proponent's statement. In: van Zutphen LFM, Balls M (eds): Animal Alternatives, Welfare and Ethics. Amsterdam: Elsevier Science B V, pp 261-265


10.	Lahm H, Hoeflich A, Rieger N, Wanke R, Wolf E (1998) Identification of transgenic mice by direct PCR analysis of lysates of epithelial cells obtained from the inner surface of the rectum. Transgenic Res 7, 131-134


11.	Mepham TB, Combes RD, Balls M, Barbieri O, Blokhuis HJ, Costa P, Crilly RE, de Cock Buning T, Delpire VC, O'Hare MJ, Houdebine L-M, van Kreijl CF, van der Meer M, Reinhardt CA, Wolf E, van Zeller A-M (1998) The use of transgenic animals in the European Union. ATLA 26, 21-43


12.	Osterrieder N. Wolf E (1998) Lessons from gene knockouts. Rev Sci Tech OIE 17, 351-364


13.	Aigner B, Pambalk K, Reichart U, Besenfelder U, Bosze Z, Renner M, Günzburg WH, Wolf E, Müller M, Brem G (1999) Species-specific alternative splicing of transgenic RNA in the mammary glands of pigs, rabbits and mice. Biochem Biophys Res Commun 257, 843-850



14.	Förster R, Schubel A, Breitfeld D, Kremmer E, Renner-Müller I, Wolf E, Lipp M (1999) CCR7 coordinates the primary immune response by guiding lymphocytes and dendritic cells to establish functional microenvironments in secondary lymphoid organs. Cell 99, 23-33



15.	Lipp M, Burgstahler R, Müller G, Pevzner V, Kremmer E, Wolf E, Förster R (2000) Functional organization of secondary lymphoid organs by the chemokine system. Curr Top Microbiol Immunol 251, 173-179


16.	Nalbantoglu J, Larochelle N, Wolf E, Karpati G, Lochmüller H, Holland PC (2001) Muscle-specific overexpression of the adenovirus primary receptor CAR overcomes low efficiency of gene transfer to mature skeletal muscle. J Virol 75, 4276-4282


17.	Thorey IS, Roth J, Regenbogen J, Halle J-P, Bittner M, Vogl T, Kaesler S, Bugnon P, Reitmaier B, Durka S, Graf A, Wöckner M, Rieger N, Konstantinow A, Wolf E, Goppelt A, Werner S (2001) The Ca2+-binding proteins S100A8 and S100A9 are encoded by novel injury-regulated genes. J Biol Chem 276, 35818-35825


18.	Wankell M, Munz B, Hübner G, Hans W, Wolf E, Goppelt A, Werner S (2001) Impaired wound healing in transgenic mice overexpressing the activin antagonist follistatin in the epidermis. EMBO J 20, 5361-5372


19.	Dunant P, Larochelle N, Thirion C, Stucka R, Ursu D, Petrof BJ, Wolf E, Lochmüller H (2003) Expression of dystrophin driven by the 1.35 kb MCK promoter ameliorates muscular dystrophy in fast, but not in slow muscles of transgenic mdx mice. Mol Ther 8, 80-89


20.	Gilch S, Wopfner F, Renner-Müller I, Kremmer E, Bauer C, Wolf E, Brem G, Groschup MH, Schätzl HM (2003) Polyclonal anti-PrP auto-antibodies induced with dimeric PrP interfere efficiently with PrPSc propagation in prion-infected cells. J Biol Chem 278, 18524-18531



21.	Hofmann A, Kessler B, Ewerling S, Weppert M, Vogg B, Ludwig H, Stojkovic M, Boelhauve M, Brem G, Wolf E, Pfeifer A (2003) Efficient transgenesis in farm animals by lentiviral vectors. EMBO Rep 4, 1054-1058


	Leheste JR, Melsen F, Wellner M, Jansen P, Schlichting U, Renner-Müller I, Andreassen TT, Wolf E, Bachmann S, Nykjaer A, Willnow TE (2003) Hypocalcemia and osteopathy in mice with kidney-specific megalin gene defect. FASEB J 17, 247-249
22.

23.	Zeitz U, Weber K, Soegiarto DW, Adamski J, Wolf E, Balling R, Erben RG (2003) Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. FASEB J 17, 509-511


24.	Leucht C, Vana K, Renner-Müller I, Lasmézas CI, Wolf E, Weiss S (2004) Knock-down of the 37-kDa laminin receptor in mouse brain by transgenic expression of specific antisense LRP RNA. Transgenic Res (in press)

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Publications by topic:

- Molecular mechanisms of mammalian growth regulation

- Biology and Biotechnology of Reproduction

- Mouse Genetics and ENU-Mutagenesis

- Mammalian Transgenic Technology

Mouse Genetics and ENU-Mutagenesis

1.	Flaswinkel H, Reth M (1992) Molecular cloning of the Ig- a subunit of the human B-cell anitgen receptor complex. Immunogenetics 36, 266-269


2.	Iglesias A, Nichogiannopoulou A, Williams SG, Flaswinkel H, Köhler G (1993) Early B cell development requires µ signaling. Eur. J. Immunol. 23, 2622-2630


3.	Flaswinkel H, Reth M (1994) Dual role of the tyrosine activation motif of the Ig-a protein during signal transduction via the B-cell antigen receptor. EMBO J. 13, 83-89

4.	Flaswinkel H, Barner M, Reth M (1995) The tyrosine activation motif (TAM) as a target of PTKs and SH2 domains. Seminars in Immunology 7, 21-27

5.	Xiao-rui Y, Flaswinkel H, Reth M, Scott D (1995) The Immunoreceptor tyrosine-based activation motif (ITAM) is required for signal pathways of receptor-mediated growth arrest and apoptosis in murine B-lymphoma cells. J Immunol 155, 652-661


6.	Torres RM, Flaswinkel H, Reth M, Rajewsky K (1996) Aberrant B cell development and immune response in mice with a compromised B-cell antigen receptor complex. Science 272, 1804-1808


7.	Bewarder N, Weinrich V, Budde P, Hartmann D, Flaswinkel H, Reth M, Frey J (1996) In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (FcgRII) phosphorylation. Mol Cell Biol 16, 4735-4743



8.	Adachi T, Flaswinkel H, Yakura H, Reth M, Tsubata T (1998) The B cell surface protein CD72 recruits the tyrosine phosphatase SHP-1 upon tyrosine phosphorylation. J Immunol 160, 4662-4665


9.	Balling R, Hrabe de Angelis M, Schughart K, Wolf E (1998) We need more mutants: plans for a large scale ENU mouse mutagenesis screen. OECD Proceedings: Novel systems for the study of human diseases, 103-111


10.	Graw J, Jung M, Löster J, Klopp N, Soewarto D, Fella C, Fuchs H, Reis A, Wolf E, Balling R, Hrabe de Angelis M (1999) Mutation in the ðbA3/A1-crystallin encoding gene Cryba1 causes a dominant cataract in the mouse. Genomics 62, 67-73


11.	Rathkolb B, Krebs O, Balling R, Hrabé de Angelis M, Wolf E (1999) Discovery and functional characterization of new genes by large scale ENU mutagenesis in mice. Arch Tierz, Dummerstorf 42, 74-85


12.	Flaswinkel H, Alessandrini A, Rathkolb B, Decker T, Kremmer E, Servatius A, Jakob T, Soewarto D, Marschall S, Fella C, Behrendt H, Ring J, Wolf E, Balling R, Hrabé de Angelis M, Pfeffer K (2000) Identification of immunological relevant phenotypes in ENU mutagenized mice. Mamm Genome 11, 526-527


13.	Fuchs H, Schughart K, Wolf E, Balling R, Hrabé de Angelis M (2000) Screening for dysmorphological abnormalities - a powerful tool to isolate new mouse mutants. Mamm Genome 11, 528-530



14.	Rathkolb B, Decker T, Fuchs E, Soewarto D, Fella C, Heffner S, Pargent W, Wanke R, Balling R, Hrabé de Angelis M, Kolb HJ, Wolf E (2000) The clinical-chemical screen in the Munich ENU Mouse Mutagenesis Project: screening for clinically relevant phenotypes. Mamm Genome 11, 543-546



15.	Rathkolb B, Fuchs E, Kolb HJ, Renner-Müller I, Krebs O, Balling R, Hrabé de Angelis M, Wolf E (2000) Large-scale N-ethyl-N-nitrosourea mutagenesis of mice - from phenotypes to genes. Exp Physiol 85.6, 635-644


16.	Rolinski B, Arnecke R, Dame T, Kreischer J, Olgemöller B, Wolf E, Balling R, Hrabé de Angelis M, Roscher AA (2000) The biochemical metabolite screen in the Munich ENU Mouse Mutagenesis Project: determination of amino acids and acylcarnitines by tandem mass spectrometry. Mamm Genome 11, 547-551


17.	Soewarto D, Fella C, Teubner A, Rathkolb B, Pargent W, Heffner S, Marschall S, Wolf E, Balling R, Hrabé de Angelis M (2000) The large-scale Munich ENU-mouse-mutagenesis screen. Mamm Genome 11, 507-510


18.	Hrabé de Angelis M, Flaswinkel H, Fuchs H, Rathkolb B, Soewarto D, Marschall S, Heffner S, Pargent W, Wuensch K, Jung M, Reis A, Richter T, Alessandrini F, Jakob T, Fuchs E, Kolb H, Kremmer E, Schaeble K, Rollinski B, Roscher A, Peters C, Meitinger T, Strom T, Steckler T, Holsboer F, Klopstock T, Gekeler F, Schindewolf C, Jung T, Avraham K, Behrendt H, Ring J, Zimmer A, Schughart K, Pfeffer K, Wolf E, Balling R (2000) Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat Genet 25, 444-447




19.	Alessandrini F Jakob T, Wolf A, Wolf E, Balling R, Hrabé de Angelis M, Ring J, Behrendt H (2001) ENU-mouse mutagenesis: generation of mouse mutants with aberrant plasma IgE levels. Int Arch Allergy Immunol 124, 25-28


20.	Graw J, Klopp N, Löster J, Soewarto D, Fuchs H, Becker-Follmann J, Reis A, Wolf E, Balling R, Hrabé de Angelis M (2001) Ethylnitrosourea-induced mutation in mice leads to the expression of a novel protein in the eye and to dominant cataracts. Genetics 157, 1313-1320



21.	Graw J, Löster J, Soewarto D, Fuchs H, Reis A, Wolf E, Balling R, Hrabé de Angelis M (2001) Aey2, a new mutation in the ðbB2-crystallin-encoding gene of the mouse. Invest Ophthalmol Vis Sci 42, 1574-1580

22.	Graw J, Loster J, Soewarto D, Fuchs H, Reis A, Wolf E, Balling R, Hrabé de Angelis M (2002) V76D mutation in a conserved ðgD-crystallin region leads to dominant cataracts in mice. Mamm Genome 13, 452-455

23.	Krebs O, Schreiner CM, Scott WJ Jr, Bell SM, Robbins DJ, Goetz JA, Alt H, Hawes N, Wolf E, Favor J (2003) Replicated anterior zeugopod (raz): a polydactylous mouse mutant with lowered Shh signaling in the limb bud. Development 130, 6037-6047



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Biology and Biotechnology of Reproduction

1.	Stojkovic M, Wolf E, Büttner M, Berg U, Charpigny G, Schmitt A, Brem G (1995) Secretion of biologically active interferon tau by in vitro-derived bovine trophoblastic tissue. Biol Reprod 53, 1500-1507


2.	Zakhartchenko V, Wolf E, Palma GA, Brem G (1995) Effect of donor embryo cell number and cell size on the efficiency of bovine embryo cloning. Mol Reprod Dev 42, 53-57


3.	Mödl J, Reichenbach H-D, Wolf E, Brem G (1996) Development of frozen-thawed porcine blastocysts in vitro and in vivo. Vet Rec 139, 208-210

4.	Zakhartchenko V, Reichenbach H-D, Riedl J, Palma GA, Wolf E, Brem G (1996) Nuclear transfer in cattle using in vivo-derived versus in vitro-produced donor embryos: effect of developmental stage. Mol Reprod Dev 44, 493-498

	Stojkovic M, Wolf E, Van Langendonckt A, Vansteenbrugge A, Charpigny G, Reinaud P, Gandolfi F, Brevini TAL, Mermillod P, Terqui M, Brem G, Massip A (1997) Correlations between chemical parameters, mitogenic activity, and embryotrophic activity of bovine oviduct-conditioned medium. Theriogenology 48, 659-673
5.


6.	Stojkovic M, Zakhartchenko V, Brem G, Wolf E (1997) Secretions of in vitro derived bovine trophoblastic vesicles support the development of bovine embryos in vitro. J Reprod Fertil 111, 191-196

7.	Wolf E, Stojkovic M, Wenigerkind H, Santl B, Prelle K, Reichenbach HD, Zakhartchenko V, Schernthaner W. Palma GA, Brem G (1997) Some factors affecting the efficiency of in vitro production of bovine embryos and related techniques. In: Li N, Chen Y (eds): Proceedings of International Conference on Animal Biotechnology. Beijing: International Academic Publishers, pp 285-291



8.	Zakhartchenko V, Stojkovic M, Brem G, Wolf E (1997) Karyoplast-cytoplast volume ratio in bovine nuclear transfer embryos: effect on the developmental potential. Mol Reprod Dev 48, 332-338


9.	Bieser B, Stojkovic M, Wolf E, Meyer H, Einspanier R (1998) Growth factors and components for extracellular proteolysis are differentially expressed during in vitro maturation of bovine cumulus-oocyte complexes. Biol Reprod 59, 801-806


10.	Durcova-Hills G, Prelle K, Müller S, Stojkovic M, Motlik J, Wolf E, Brem G (1998) Primary culture of porcine PGCs requires LIF and porcine membrane-bound stem cell factor. Zygote 6, 271-275


11.	Kölle S, Sinowatz F, Boie G, Palma G, Stojkovic M, Wolf E (1998) Topography of growth hormone receptor expression in the bovine embryo. Histochem Cell Biol 109, 417-419


12.	Santl B, Wenigerkind H, Schernthaner W, Mödl J, Stojkovic M, Prelle K, Holtz W, Brem G, Wolf E (1998) Comparison of ultrasound-guided vs laparoscopic transvaginal ovum pick-up (OPU) in Simmental heifers. Theriogenology 50, 89-100


13.	Steinborn R, Zakhartchenko V, Jelyazkov J, Klein D, Wolf E, Müller M, Brem G (1998) Composition of parental mitochondrial DNA in cloned bovine embryos. FEBS Lett 426, 352-356



14.	Steinborn R, Zakhartchenko V, Wolf E, Müller M, Brem G (1998) Non-balanced mix of mitochondrial DNA in cloned cattle produced by cytoplast-blastomere fusion. FEBS Lett 426, 357-361


15.	Stojkovic M, Büttner M, Zakhartchenko V, Brem G, Wolf E (1998) A reliable procedure for differential staining of in vitro produced bovine blastocysts: comparison of tissue culture medium 199 and Ménézo's B2 medium. Anim Reprod Sci 50, 1-9


16.	Wolf E, Zakhartchenko V, Brem G (1998) Nuclear transfer in mammals: recent developments and future perspectives. J Biotechnol 65, 99-110

17.	Wolf E, Boxhammer K, Brem G, Prelle K, Reichenbach H-D, Reischl J, Santl B, Schernthaner W, Stojkovic M, Wenigerkind H, Zakhartchenko V (1998) Recent developments in the in vitro production and cloning of bovine embryos. Arq Fac Vet UFRGS 26 Supl, 160-178


18.	Alberio R, Palma G, Stojkovic M, Brem G, Wolf E (1999) Effects and interactions of bovine growth hormone with FSH on the kinetics of nuclear maturation of bovine oocytes and development of in vitro produced embryos. Macedonian J Reprod 5, 129-137



19.	Hoeflich A, Reichenbach R-D, Schwartz J, Grupp T, Weber MM, Föll J, Wolf E (1999) Insulin-like growth factors and IGF-binding proteins in bovine seminal plasma. Dom Anim Endocrinol 17, 39-51



20.	Müller S, Prelle K, Rieger N, Petznek H, Lassnig C, Luksch U, Aigner B, Baetscher M, Wolf E, Müller M, Brem G (1999) Chimeric pigs following blastocyst injection of transgenic porcine primordial germ cells. Mol Reprod Dev 54, 244-254


21.	Prelle K, Vasiliev I, Vasilieva S, Wolf E, Wobus A (1999) Establishment of pluripotent cell lines in vertebrates. Cells Tissues Organs 165, 220-236

22.	Reischl J, Prelle K, Schöl H, Neumüller C, Einspanier R, Sinowatz F, Wolf E (1999) Factors affecting proliferation and dedifferentiation of primary bovine epithelial cells in vitro. Cell Tissue Res 296, 371-383


23.	Schernthaner W, Wenigerkind H, Stojkovic M, Palma GA, Mödl J, Wolf E, Brem G (1999) Pregnancy rate after ultrasound-guided follicle aspiration in nonlactating cows from different breeds. Zentralbl Veterinärmed A 46, 33-37


24.	Stojkovic M, Motlik J, Kölle S, Zakhartchenko V, Alberio R, Sinowatz F, Wolf E (1999) Cell-cycle control and oocyte maturation: review of literature. Reprod Dom Anim 34, 335-342


25.	Stojkovic M, Westesen K, Zakhartchenko V, Stojkovic P, Boxhammer K, Wolf E (1999) Coenzyme Q10 in submicron-sized dispersion improves development, hatching, cell proliferation, and adenosine triphosphate content of in vitro-produced bovine embryos. Biol Reprod 61, 541-547



26.	Stojkovic M, Büttner M, Zakhartchenko V, Riedl J, Reichenbach H-D, Wenigerkind H, Brem G, Wolf E (1999) Secretion of interferon-tau by bovine embryos in long-term culture: comparison of in vivo derived, in vitro produced, nuclear transfer and demi-embryos. Anim Reprod Sci 55, 151-162



27.	Stojkovic M, Zakhartchenko V, Stojkovic P, Wolf E (1999) In vitro culture of bovine embryos: from co-culture to serum-free media with the same efficiency. Macedonian J Reprod 5, 119-128


28.	Wolf E, Stojkovic M, Schernthaner W, Prelle K, Zakhartchenko V, Wenigerkind H, Reichenbach H-D (1999) Biotechnology of reproduction - progress and perspectives. In: Wensing T (ed) Production diseases in farm animals. Wageningen: Wageningen Pers (ISBN 90-74134-60-2), pp 90-97


29.	Zakhartchenko V, Durcova-Hills G, Schernthaner W, Stojkovic M, Reichenbach H-D, Müller S, Prelle K, Steinborn R, Müller M, Wolf E, Brem G (1999a) Potential of fetal germ cells for nuclear transfer in cattle. Mol Reprod Dev 52, 421-426


30.	Zakhartchenko V, Durcova-Hills G, Stojkovic M, Schernthaner W, Prelle K, Steinborn R, Müller M, Brem G, Wolf E (1999b) Effects of serum starvation and re-cloning on the efficiency of nuclear transfer using bovine fetal fibroblasts. J Reprod Fertil 115, 325-331


31.	Zakhartchenko V, Alberio R, Stojkovic M, Prelle K, Schernthaner W, Stojkovic P, Wenigerkind H, Wanke R, Düchler M, Steinborn R, Müller M, Brem G, Wolf E (1999c) Adult cloning in cattle: potential of nuclei from a permanent cell line and from primary cultures. Mol Reprod Dev 54, 264-272


32.	Alberio R, Kubelka M, Zakhartchenko V, Hajdúch M, Wolf E, Motlik J (2000) Activation of bovine oocytes by specific inhibition of cyclin dependent kinases. Mol Reprod Dev 55, 422-432


33.	Alberio R, Motlik J, Stojkovic M, Wolf E, Zakhartchenko V (2000) Behavior of M-phase synchronized blastomeres after nuclear transfer in cattle. Mol Reprod Dev 57, 37-47


34.	Hyttel P, Laurincik J, Viuff D, Fair T, Zakhartchenko V, Rosenkranz C, Avery B, Rath D, Niemann H, Thomsen PD, Schellander K, Callesen H, Wolf E, Ochs RL, Greve T (2000) Activation of ribosomal RNA genes in preimplantation cattle and swine embryos. Anim Reprod Sci 60-61, 49-60


35.	Laurincik J, Zakhartchenko V, Avery B, Stojkovic M, Brem G, Wolf E, Müller M, Hyttel P (2000) Activation of ribosomal RNA genes in pre-implantation in vitro-produced and nuclear transfer embryos. Reprod Dom Anim 35, 255-259


36.	Steinborn R, Schinogl P, Zakhartchenko V, Achmann R, Schernthaner W, Stojkovic M, Wolf E, Müller M, Brem G (2000) Mitochondrial DNA heteroplasmy in cloned cattle produced by fetal and adult cell cloning. Nat Genet 25, 255-257


37.	Stojkovic M, Büttner M, Zakhartchenko V, Wolf E (2000) Maternal recognition of pregnancy in domestic ruminants. Macedonian J Reprod 6, 5-10


38.	Stojkovic M, Kölle S, Zakhartchenko V, Stojkovic P, Sinowatz F, Wolf E (2000) Effects of estrous cow serum/bovine serum albumin on early cleavage, blastocyst rate, cell number, and ultrastructural configuration of in vitro produced bovine embryos. Adv Reprod 5, 35-44

39.	Suttner R, Zakhartchenko V, Stojkovic P, Müller S, Alberio R, Brem G, Wolf E, Stojkovic M (2000) Intracytoplasmic sperm injection in bovine: effects of oocyte activation, sperm pretreatment and injection technique. Theriogenology 54, 935-948


40.	Wobus AM, Wolf E, Beier HM (2000) Embryonic stem cells and nuclear transfer strategies - present state and future prospects. Cells Tissues Organs 166, 1-5

41.	Wolf E, Schernthaner W, Zakhartchenko V, Prelle K, Stojkovic M, Brem G (2000) Transgenic technology in farm animals - progress and perspectives. Exp Physiol 85.6, 615-625


42.	Alberio R, Brero A, Motlik, J, Cremer T, Wolf E, Zakhartchenko V (2001) Remodeling of donor nuclei, DNA-synthesis, and ploidy of bovine cumulus cell nuclear transfer embryos: effect of activation protocol. Mol Reprod Dev 59, 371-379


43.	Alberio R, Zakhartchenko V, Motlik J, Wolf E (2001) Mammalian oocyte activation: lessons from the sperm and implications in nuclear transfer. Int J Dev Biol 45, 797-809



44.	Dean W, Santos F, Stojkovic M, Zakhartchenko V, Walter J, Wolf E, Reik W (2001) Conservation of methylation reprogramming in mammalian embryos: aberrant reprogramming in cloned embryos. PNAS 98, 13734-13738


45.	Freistedt P, Stojkovic M, Wolf E (2001) Efficient in vitro production of cat embryos in modified synthetic oviduct fluid medium: effects of season and ovarian status. Biol Reprod 65, 9-13


46.	Freistedt P, Stojkovic P, Wolf E, Stojkovic M (2001) Energy status of nonmatured and in vitro-matured domestic cat oocytes and of different stages of in vitro-produced embryos: enzymatic removal of the zona pellucida increases adenosine triphosphate content and total cell number of blastocysts. Biol Reprod 65, 793-798


47.	Hirai M, Boersma A, Hoeflich A, Wolf E, Föll J, Aumüller R, Braun J (2001) Objectively measured sperm motility and sperm head morphometry in boars (Sus scrofa): relation to fertility and seminal plasma growth factors. J Androl 22, 104-110


48.	Kölle S, Stojkovic M, Prelle K, Waters M, Wolf E, Sinowatz F (2001) Growth hormone (GH)/growth hormone receptor expression and GH-mediated effects during early bovine embryogenesis. Biol Reprod 64, 1826-1834


49.	Prelle K, Stojkovic M, Boxhammer K, Motlik J, Ewald D, Arnold GJ, Wolf E (2001) IGF-I and Long R3IGF-I differently affect development and messenger RNA abundance for IGF-binding proteins and type I IGF receptors in in vitro produced bovine embryos. Endocrinology 142, 1309-1316


50.	Stojkovic M, Machado SA, Stojkovic P, Zakhartchenko V, Hutzler P, Goncalves PB, Wolf E (2001) Mitochondrial distribution and adenosine triphosphate-content of bovine oocytes before and after in vitro maturation: correlation with morphological criteria and developmental capacity after in vitro fertilization and culture. Biol Reprod 64, 904-909


51.	Zakhartchenko V, Mueller S, Alberio R, Schernthaner W, Stojkovic M, Wenigerkind H, Wanke R, Lassnig C, Mueller M, Wolf E, Brem G (2001) Nuclear transfer in cattle with non-transfected and transfected fetal or cloned transgenic fetal and postnatal fibroblasts. Mol Reprod Dev 60, 362 369


52.	Brüggerhoff K, Zakhartchenko V, Wenigerkind H, Reichenbach H-D, Prelle K, Schernthaner W, Alberio R, Küchenhoff H, Stojkovic M, Brem G, Hiendleder S, Wolf E (2002) Bovine somatic cell nuclear transfer using recipient oocytes recovered by ovum pick-up: effect of maternal lineage of oocyte donors. Biol Reprod 66, 367-373


53.	Einspanier R, Schönfelder M, Müller K, Stojkovic M, Kosmann M, Wolf E, Schams D (2002) Expression of the vascular endothelial growth factor (VEGF)-system and first biological effects of VEGF during in vitro maturation of bovine cumulus oocyte complexes (COC). Mol Reprod Dev 62, 29-36


54.	Kölle S, Stojkovic M, Boie G, Wolf E, Sinowatz F (2002) Growth hormone inhibits apoptosis in in vitro produced bovine embryos. Mol Reprod Dev 61, 180-186

55.	Laurincik J, Zakhartchenko V, Stojkovic M, Brem G, Wolf E, Müller M, Ochs RL, Hyttel P (2002) Nucleolar protein allocation and ultrastructure in bovine embryos produced by nuclear transfer from granulosa cells. Mol Reprod Dev 61, 477-487


56.	Motlik J, Alberio R, Zakhartchenko V, Stojkovic M, Kubelka M, Wolf E (2002) The effect of activation of mammalian oocytes on remodeling of donor nuclei after nuclear transfer. Cloning Stem Cells 4, 245-252



57.	Ott M, Schernthaner W, Sinowatz F, Wolf E (2002) Effects of bovine serum albumin and estrous cow serum on development and ultrastructure of in vitro-produced porcine embryos. Anat Histol Embryol 31, 151-157


58.	Prelle K, Zink N, Wolf E (2002) Pluripotent stem cells - model of embryonic development, tool for gene targeting, and basis of cell therapy. Anat Histol Embryol 31, 169-186


59.	Rief S, Sinowatz F, Stojkovic M, Einspanier R, Wolf E, Prelle K (2002) A novel co-culture system affects development, metabolism and gene expression of in vitro produced bovine embryos. Reproduction 124, 543-556


60.	Stojkovic M, Kölle S, Peinl S, Stojkovic P, Zakhartchenko V, Thompson JG, Wenigerkind H, Reichenbach H-D, Sinowatz F, Wolf E (2002) Effects of high concentrations of hyaluronan in culture medium on development and survival rates of fresh and frozen-thawed bovine embryos produced in vitro. Reproduction 124, 141-153

61.	Wolf E (2002) Cloning of animals - perspectives for biomedical research. Exp Toxicol Pathol 54, 161-162

62.	Bauersachs S, Blum H, Mallok S, Wenigerkind H, Rief S, Prelle K, Wolf E (2003) Regulation of ipsilateral and contralateral bovine oviduct epithelial cell function in the post-ovulation period - a transcriptomics approach. Biol Reprod 68, 1170-1177


63.	Hiendleder S, Zakhartchenko V, Wenigerkind H, Reichenbach H-D, Brüggerhoff K, Prelle K, Brem G, Stojkovic M, Wolf E (2003) Heteroplasmy in bovine fetuses produced by intra- and intersubspecific somatic cell nuclear transfer: neutral segregation of nuclear donor mitochondrial DNA in various tissues and evidence for recipient cow mitochondria in fetal blood. Biol Reprod 68, 159-166




64.	Hiendleder S, Wolf E (2003) The mitochondrial genome in embryo technologies. Reprod Dom Anim 38, 290-304

65.	Kölle S, Stojkovic M, Boie G, Wolf E, Sinowatz F (2003) Growth hormone-related effects on apoptosis, mitosis and expression of connexin 43 in IVM cumulus-oocyte-complexes. Biol Reprod 68, 1584-1589

66.	Laurincik J, Schmoll F, Mahabir E, Schneider H, Stojkovic M, Zakhartchenko V, Prelle K, Hendrixen PJM, Voss PLAM, Moeszlacher GG, Avery B, Dieleman SJ, Besenfelder U, Müller M, Ochs RL, Wolf E, Schellander K, Maddox-Hyttel P (2003) Nucleolar proteins and ultrastructure in bovine in vivo developed, in vitro produced, and parthenogenetic cleavage-stage embryos. Mol Reprod Dev 65, 73-85

67.	Santos F, Zakhartchenko V, Stojkovic M, Peters A, Jenuwein T, Wolf E, Reik W, Dean W (2003) Epigenetic marking correlates with developmental potential in cloned bovine preimplantation embryos. Curr Biol 13, 1116-1121
68.	Shi, W, Zakhartchenko V, Wolf E (2003) Mammalian nuclear transfer and epigenetic reprogramming. Differentiation 71, 91-113
69.	Shi W, Hoeflich A, Flaswinkel H, Stojkovic M, Wolf E, Zakhartchenko V (2003) Induction of a senescent-like phenotype does not confer the ability of bovine immortal cells to support the development of nuclear transfer embryos. Biol Reprod 69, 301-309
70.	Stojkovic M, Krebs O, Kölle S, Prelle K, Assmann V, Zakhartchenko V, Sinowatz F, Wolf E (2003) Developmental regulation of hyaluronan-binding protein (RHAMM/ IHABP) expression in early bovine embryos. Biol Reprod 68, 60-66
71.	Wolf E, Arnold GJ, Bauersachs S, Beier HM, Blum H, Einspanier R, Fröhlich T, Herrler A, Hiendleder S, Kölle S, Prelle K, Reichenbach H-D, Stojkovic M, Wenigerkind H, Sinowatz F (2003) Embryo-maternal communication in bovine - strategies for deciphering a complex cross-talk. Reprod Dom Anim 38, 276-289

72.	Bauersachs S, Rehfeld S, Ulbrich S, Mallok S, Prelle K, Wenigerkind H, Einspanier R, Blum H, Wolf E (2004) Monitoring gene expression changes in bovine oviduct epithelial cells during the oestrous cycle. J Mol Endocrinol (accepted)

73.	Hiendleder S, Prelle K, Brüggerhoff K, Reichenbach H-D, Wenigerkind H, Bebbere D, Stojkovic M, Müller S, Brem G, Zakhartchenko V, Wolf E (2004) Nuclear-cytoplasmic interactions affect in utero developmental capacity, phenotype and cellular metabolism of bovine nuclear transfer fetuses. Biol Reprod (in press

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