Perspectives Series: Molecular Medicine in Genetically Engineered Animals

Advances in biotechnology over the last ten years have made it possible for the researcher to alter gene expression in vivo in many diverse ways (1). With the establishment of embryonic stem (ES) 1 cell technology (2), more subtle and precise alterations can now be achieved than were previously possible using microinjection techniques. However, to date germline transmission has only been achieved with mouse ES cells, and microinjection continues to be the method most widely used for other species. While the mouse has a number of advantages, not least the depth of our knowledge of its genetics, other species are being increasingly used for transgenic studies due to their greater suitability for addressing specific questions. We will briefly review the application of transgenic technology to nonmurine species as it stands at present, with par

[1]  K. Rajewsky,et al.  Aberrant B Cell Development and Immune Response in Mice with a Compromised BCR Complex , 1996, Science.

[2]  J. Heath,et al.  Cardiotrophin-1 Activates a Distinct Form of Cardiac Muscle Cell Hypertrophy , 1996, The Journal of Biological Chemistry.

[3]  R. Evans,et al.  Ecdysone-inducible gene expression in mammalian cells and transgenic mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[4]  P. Angrand,et al.  Regulation of Cre recombinase activity by the synthetic steroid RU 486. , 1996, Nucleic acids research.

[5]  U. Certa,et al.  Efficient control of gene expression by single step integration of the tetracycline system in transgenic mice , 1996, Nature Biotechnology.

[6]  K. Chien,et al.  Cardiotrophin-1 displays early expression in the murine heart tube and promotes cardiac myocyte survival. , 1996, Development.

[7]  F. Sablitzky,et al.  Inducible site-directed recombination in mouse embryonic stem cells. , 1996, Nucleic acids research.

[8]  L. Tabak,et al.  T-cell-specific deletion of a polypeptide N-acetylgalactosaminyl-transferase gene by site-directed recombination. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[9]  A. Bradley,et al.  Chromosome engineering in mice , 1995, Nature.

[10]  J. Wilson,et al.  Gene therapy for cystic fibrosis: challenges and future directions. , 1995, The Journal of clinical investigation.

[11]  D. Rader,et al.  A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia , 1995, Nature Medicine.

[12]  S. Rosenberg,et al.  T Lymphocyte-Directed Gene Therapy for ADA− SCID: Initial Trial Results After 4 Years , 1995, Science.

[13]  L. Zon,et al.  Developmental biology of hematopoiesis. , 1995, Blood.

[14]  S. Orkin,et al.  Transcription factor GATA-1 permits survival and maturation of erythroid precursors by preventing apoptosis. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Steinberg,et al.  Effect of the antioxidant N,N'-diphenyl 1,4-phenylenediamine (DPPD) on atherosclerosis in apoE-deficient mice. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[16]  K. Weinberg,et al.  Engraftment of gene–modified umbilical cord blood cells in neonates with adenosine deaminase deficiency , 1995, Nature Medicine.

[17]  K. Chien,et al.  Ventricular Expression of a MLC-2v-ras Fusion Gene Induces Cardiac Hypertrophy and Selective Diastolic Dysfunction in Transgenic Mice (*) , 1995, The Journal of Biological Chemistry.

[18]  M. Moskowitz,et al.  Hypertension in mice lacking the gene for endothelial nitric oxide synthase , 1995, Nature.

[19]  M Aguet,et al.  Inducible gene targeting in mice , 1995, Science.

[20]  J. Taylor,et al.  Apolipoprotein B mRNA-editing protein induces hepatocellular carcinoma and dysplasia in transgenic animals. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[21]  A. Joyner,et al.  Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2. , 1995, Science.

[22]  R. Evans,et al.  Retinoid-dependent pathways suppress myocardial cell hypertrophy. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. C. Lin,et al.  Heart and lung disease in engineered mice , 1995, Nature Medicine.

[24]  B. Abella,et al.  Generation and characterization of a ΔF508 cystic fibrosis mouse model , 1995, Nature Genetics.

[25]  Klaus Rajewsky,et al.  Impairment of T-cell-dependent B-cell responses and B-l cell development in CD19-deficient mice , 1995, Nature.

[26]  P. Chambon,et al.  Conditional site-specific recombination in mammalian cells using a ligand-dependent chimeric Cre recombinase. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[27]  S. Eaton,et al.  Apical, basal, and lateral cues for epithelial polarization , 1995, Cell.

[28]  Janet Rossant,et al.  Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice , 1995, Nature.

[29]  R. Nagai,et al.  Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1. , 1995, The Journal of clinical investigation.

[30]  A. Berns,et al.  Adenosine–deaminase–deficient mice die perinatally and exhibit liver–cell degeneration, atelectasis and small intestinal cell death , 1995, Nature Genetics.

[31]  M. Gossen,et al.  Transcriptional activation by tetracyclines in mammalian cells. , 1995, Science.

[32]  C. Logie,et al.  Ligand-regulated site-specific recombination. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[33]  I. Bernstein,et al.  Generation of hematopoietic colony-forming cells from embryonic stem cells: synergy between a soluble factor from NIH-3T3 cells and hematopoietic growth factors. , 1995, Blood.

[34]  M. Mehtali,et al.  Human immunodeficiency virus type 1 infection of human CD4-transgenic rabbits. , 1995, The Journal of general virology.

[35]  T. Kishimoto,et al.  Continuous activation of gp130, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[36]  J. Charles Jennette,et al.  Male–female differences in fertility and blood pressure in ACE-deficient mice , 1995, Nature.

[37]  J. Gardin,et al.  Echocardiographic assessment of left ventricular mass and systolic function in mice. , 1995, Circulation research.

[38]  N. Cary,et al.  TISSUE EXPRESSION OF HUMAN COMPLEMENT INHIBITOR, DECAY‐ACCELERATING FACTOR, IN TRANSGENIC PIGS A POTENTIAL APPROACH FOR PREVENTING XENOGRAFT REJECTION , 1995, Transplantation.

[39]  J. Platt,et al.  Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury , 1995, Nature Medicine.

[40]  M. Sanguinetti,et al.  A mechanistic link between an inherited and an acquird cardiac arrthytmia: HERG encodes the IKr potassium channel , 1995, Cell.

[41]  H. Ertl,et al.  Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses , 1995, Journal of virology.

[42]  D. Gottlieb,et al.  Embryonic stem cells express neuronal properties in vitro. , 1995, Developmental biology.

[43]  D. Porteous,et al.  Lung disease in the cystic fibrosis mouse exposed to bacterial pathogens , 1995, Nature Genetics.

[44]  H. S. Kim,et al.  Genetic control of blood pressure and the angiotensinogen locus. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[45]  B L Langille,et al.  Cardiac malformation in neonatal mice lacking connexin43. , 1995, Science.

[46]  T. Kenakin,et al.  Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the β2-adrenoceptor , 1995, Nature.

[47]  E. Green,et al.  A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome , 1995, Cell.

[48]  N. Sarvetnick,et al.  Cellular and humoral immune responses to adenoviral vectors containing factor IX gene: tolerization of factor IX and vector antigens allows for long-term expression. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[49]  K. Chien,et al.  Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[50]  O. Smithies,et al.  Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension , 1995, Science.

[51]  S. Orkin,et al.  Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL , 1995, Nature.

[52]  S. Orkin,et al.  Rescue of GATA-1-deficient embryonic stem cells by heterologous GATA-binding proteins , 1995, Molecular and cellular biology.

[53]  A. Cumano,et al.  Emergence of multipotent hemopoietic cells in the yolk sac and paraaortic splanchnopleura in mouse embryos, beginning at 8.5 days postcoitus. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[54]  M. Wiles,et al.  Evidence for involvement of activin A and bone morphogenetic protein 4 in mammalian mesoderm and hematopoietic development , 1995, Molecular and cellular biology.

[55]  J. Whitsett,et al.  Correction of lethal intestinal defect in a mouse model of cystic fibrosis by human CFTR. , 1994, Science.

[56]  K. Rajewsky,et al.  Cre-loxP-mediated gene replacement: a mouse strain producing humanized antibodies , 1994, Current Biology.

[57]  L. Matis,et al.  Expression of a functional human complement inhibitor in a transgenic pig as a model for the prevention of xenogeneic hyperacute organ rejection. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[58]  P. Nielsen,et al.  In vitro generation of lymphoid precursors from embryonic stem cells. , 1994, The EMBO journal.

[59]  R. Lefkowitz,et al.  Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[60]  M. Gossen,et al.  Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[61]  J. Vonesch,et al.  Genetic analysis of RXRα developmental function: Convergence of RXR and RAR signaling pathways in heart and eye morphogenesis , 1994, Cell.

[62]  R. Crystal,et al.  Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis , 1994, Nature Genetics.

[63]  T. Honjo,et al.  Generation of lymphohematopoietic cells from embryonic stem cells in culture. , 1994, Science.

[64]  E. Rubin,et al.  Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice. , 1994, The Journal of clinical investigation.

[65]  H. Ertl,et al.  MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses. , 1994, Immunity.

[66]  M. Evans,et al.  The Oncogenic Cysteine-rich LIM domain protein Rbtn2 is essential for erythroid development , 1994, Cell.

[67]  Robert A. Weinberg,et al.  Tumour predisposition in mice heterozygous for a targeted mutation in Nf1 , 1994, Nature Genetics.

[68]  T. Braun,et al.  ES-cells carrying two inactivated myf-5 alleles form skeletal muscle cells: activation of an alternative myf-5-independent differentiation pathway. , 1994, Developmental biology.

[69]  A M Wobus,et al.  Muscle cell differentiation of embryonic stem cells reflects myogenesis in vivo: developmentally regulated expression of myogenic determination genes and functional expression of ionic currents. , 1994, Developmental biology.

[70]  James M. Wilson,et al.  Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosis , 1994, Nature Genetics.

[71]  K. Rajewsky,et al.  Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. , 1994, Science.

[72]  Shylendra Kumar,et al.  Milk composition and lactation of beta-casein-deficient mice. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[73]  N. First,et al.  Production of calves by transfer of nuclei from cultured inner cell mass cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[74]  Christine E. Seidman,et al.  α-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: A disease of the sarcomere , 1994, Cell.

[75]  T. Honjo,et al.  Lineage marker-negative lymphocyte precursors derived from embryonic stem cells in vitro differentiate into mature lymphocytes in vivo. , 1994, International immunology.

[76]  G. Keller,et al.  Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells. , 1994, Genes & development.

[77]  D. Absher,et al.  Gq- and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following alpha 1-adrenergic stimulation. , 1994, The Journal of biological chemistry.

[78]  R. Evans,et al.  RXR alpha mutant mice establish a genetic basis for vitamin A signaling in heart morphogenesis. , 1994, Genes & development.

[79]  M. Solomon,et al.  Lipid composition of carcass tissue from transgenic pigs expressing a bovine growth hormone gene. , 1994, Journal of animal science.

[80]  N. Copeland,et al.  Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. , 1994, Genes & development.

[81]  D. Brenin,et al.  Pluripotent embryonic stem cells from the rat are capable of producing chimeras. , 1994, Developmental biology.

[82]  G. Johnson,et al.  Magnetic resonance microscopy of mouse embryos. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[83]  R. Lefkowitz,et al.  Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor. , 1994, Science.

[84]  V. Ord,et al.  ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis. Demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[85]  James M. Wilson,et al.  Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia , 1994, Nature Genetics.

[86]  J Ross,et al.  Molecular and physiological alterations in murine ventricular dysfunction. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[87]  R. Jaenisch,et al.  Double replacement: strategy for efficient introduction of subtle mutations into the murine Col1a-1 gene by homologous recombination in embryonic stem cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[88]  D. Ow,et al.  Cre recombinase-mediated site-specific recombination between plant chromosomes. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[89]  R E Jacobs,et al.  Magnetic resonance microscopy of embryonic cell lineages and movements. , 1994, Science.

[90]  A. Schnieke,et al.  Use of double-replacement gene targeting to replace the murine alpha-lactalbumin gene with its human counterpart in embryonic stem cells and mice , 1994, Molecular and cellular biology.

[91]  M. Rudnicki,et al.  MyoD or Myf-5 is required for the formation of skeletal muscle , 1993, Cell.

[92]  G. Lyons,et al.  In vitro chamber specification during embryonic stem cell cardiogenesis. Expression of the ventricular myosin light chain-2 gene is independent of heart tube formation. , 1993, The Journal of biological chemistry.

[93]  A. Colman,et al.  Transgenic Livestock as Bioreactors: Stable Expression of Human Alpha-1-Antitrypsin by a Flock of Sheep , 1993, Nature Biotechnology.

[94]  L. Mullins,et al.  Transgenesis in nonmurine species. , 1993, Hypertension.

[95]  J. Breslow Transgenic mouse models of lipoprotein metabolism and atherosclerosis. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[96]  S. Fazio Recent insights into the pathogenesis of type III hyperlipoproteinemia. , 1993, Trends in cardiovascular medicine.

[97]  R. Hammer,et al.  Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. , 1993, The Journal of clinical investigation.

[98]  A. Müller,et al.  ES cells have only a limited lymphopoietic potential after adoptive transfer into mouse recipients. , 1993, Development.

[99]  A. Müller,et al.  An early pre-liver intraembryonic source of CFU-S in the developing mouse , 1993, Nature.

[100]  J. García-Porrero,et al.  Para-aortic splanchnopleura from early mouse embryos contains B1a cell progenitors , 1993, Nature.

[101]  K. Rajewsky,et al.  Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting , 1993, Cell.

[102]  P. Howles,et al.  Developmental analysis of tropomyosin gene expression in embryonic stem cells and mouse embryos , 1993, Molecular and cellular biology.

[103]  T. Mcclanahan,et al.  Hematopoietic growth factor receptor genes as markers of lineage commitment during in vitro development of hematopoietic cells [see comments] , 1993 .

[104]  R. Frants,et al.  Transgenic mice carrying the apolipoprotein E3-Leiden gene exhibit hyperlipoproteinemia. , 1993, The Journal of biological chemistry.

[105]  V. Stewart,et al.  RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[106]  K. Chien Molecular advances in cardiovascular biology. , 1993, Science.

[107]  B. Sauer,et al.  Genomic targeting with purified Cre recombinase. , 1993, Nucleic acids research.

[108]  S. Nishikawa,et al.  Expression and function of c-Kit in fetal hemopoietic progenitor cells: transition from the early c-Kit-independent to the late c-Kit-dependent wave of hemopoiesis in the murine embryo. , 1993, Development.

[109]  K. Rajewsky,et al.  Shutdown of class switch recombination by deletion of a switch region control element , 1993, Science.

[110]  S. Powers,et al.  HRas-dependent pathways can activate morphological and genetic markers of cardiac muscle cell hypertrophy. , 1993, The Journal of biological chemistry.

[111]  M. Sands,et al.  Reversal of pathology in murine mucopolysaccharidosis type VII by somatic cell gene transfer , 1992, Nature.

[112]  E. Rubin,et al.  Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells , 1992, Cell.

[113]  N. Maeda,et al.  Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. , 1992, Science.

[114]  W. Risau,et al.  Induction of vasculogenesis and hematopoiesis in vitro. , 1992, Development.

[115]  J. Gutiérrez-Ramos,et al.  In vitro differentiation of embryonic stem cells into lymphocyte precursors able to generate T and B lymphocytes in vivo. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[116]  Wendy L. Kimber,et al.  Cystic fibrosis in the mouse by targeted insertional mutagenesis , 1992, Nature.

[117]  B. Birren,et al.  Cloning and stable maintenance of 300-kilobase-pair fragments of human DNA in Escherichia coli using an F-factor-based vector. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[118]  B. Koller,et al.  An Animal Model for Cystic Fibrosis Made by Gene Targeting , 1992, Science.

[119]  J. Marth,et al.  Tissue- and site-specific DNA recombination in transgenic mice. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[120]  L. Hennighausen,et al.  Matrix-attachment regions can impart position-independent regulation of a tissue-specific gene in transgenic mice. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[121]  B. Mosinger,et al.  Targeted oncogene activation by site-specific recombination in transgenic mice. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[122]  M. Gossen,et al.  Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[123]  E. Ginns,et al.  Animal model of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase gene , 1992, Nature.

[124]  B. Hogan,et al.  DVR-4 (bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction. , 1992, Development.

[125]  J. Smith,et al.  Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development. , 1992, Development.

[126]  G. Keller,et al.  Rescue of erythroid development in gene targeted GATA–1− mouse embryonic stem cells , 1992, Nature Genetics.

[127]  J. Seidman,et al.  Production of homozygous mutant ES cells with a single targeting construct , 1992, Molecular and cellular biology.

[128]  B. Sauer,et al.  A positive selection vector for cloning high molecular weight DNA by the bacteriophage P1 system: improved cloning efficacy. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[129]  M. Katsuki,et al.  Overexpression of apolipoprotein E in transgenic mice: marked reduction in plasma lipoproteins except high density lipoprotein and resistance against diet-induced hypercholesterolemia. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[130]  B. Sauer,et al.  Identification of cryptic lox sites in the yeast genome by selection for Cre-mediated chromosome translocations that confer multiple drug resistance. , 1992, Journal of molecular biology.

[131]  V L Bautch,et al.  Embryonic stem cell-derived cystic embryoid bodies form vascular channels: an in vitro model of blood vessel development. , 1992, Development.

[132]  M. Perricaudet,et al.  In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epithelium , 1992, Cell.

[133]  J. Wilson,et al.  Long-term improvement of hypercholesterolemia after ex vivo gene therapy in LDLR-deficient rabbits. , 1991, Science.

[134]  T. Doetschman,et al.  Myosin heavy chain gene expression in mouse embryoid bodies. An in vitro developmental study. , 1991, The Journal of biological chemistry.

[135]  S. Schwartz,et al.  Angioblast differentiation and morphogenesis of the vascular endothelium in the mouse embryo. , 1991, Developmental biology.

[136]  J. Vitale,et al.  Transgenic Production of a Variant of Human Tissue-Type Plasminogen Activator in Goat Milk: Generation of Transgenic Goats and Analysis of Expression , 1991, Bio/Technology.

[137]  E. Wagner,et al.  Early fetal hematopoietic development from in vitro differentiated embryonic stem cells. , 1991, The New biologist.

[138]  A. Monaco,et al.  Yeast artificial chromosome libraries containing large inserts from mouse and human DNA. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[139]  H. Snodgrass,et al.  Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression. , 1991, Genes & development.

[140]  M. Capecchi,et al.  Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5 , 1991, Nature.

[141]  R. Krumlauf,et al.  Introduction of a subtle mutation into the Hox-2.6 locus in embryonic stem cells , 1991, Nature.

[142]  G. Wahl,et al.  Recombinase-mediated gene activation and site-specific integration in mammalian cells. , 1991, Science.

[143]  O. Smithies,et al.  Testing an "in-out" targeting procedure for making subtle genomic modifications in mouse embryonic stem cells , 1991, Molecular and cellular biology.

[144]  G. Keller,et al.  Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. , 1991, Development.

[145]  S. Orkin,et al.  Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1 , 1991, Nature.

[146]  K. Baker,et al.  Cardiac Hypertrophy: Mechanical, Neural, and Endocrine Dependence , 1991 .

[147]  A. Berns,et al.  Consecutive inactivation of both alleles of the pim-1 proto-oncogene by homologous recombination in embryonic stem cells , 1990, Nature.

[148]  F. Grosveld,et al.  An in vitro globin gene switching model based on differentiated embryonic stem cells. , 1990, Genes & development.

[149]  R. Hammer,et al.  Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β 2m: An animal model of HLA-B27-associated human disorders , 1990, Cell.

[150]  D. Wotton,et al.  A 3′ transcriptional enhancer regulates tissue‐specific expression of the human CD2 gene. , 1990, The EMBO journal.

[151]  J. Seidman,et al.  A molecular basis for familial hypertrophic cardiomyopathy: A β cardiac myosin heavy chain gene missense mutation , 1990, Cell.

[152]  S. Solomon,et al.  A molecular basis for familial hypertrophic cardiomyopathy: An α β cardiac myosin heavy chain hybrid gene , 1990, Cell.

[153]  A. E. Sippel,et al.  Tissue specific and position independent expression of the complete gene domain for chicken lysozyme in transgenic mice. , 1990, The EMBO journal.

[154]  P. Howles,et al.  Mouse embryonic stem cells express the cardiac myosin heavy chain genes during development in vitro. , 1990, The Journal of biological chemistry.

[155]  N. Henderson,et al.  Targeted insertion of exogenous DNA into the eukaryotic genome by the Cre recombinase. , 1990, The New biologist.

[156]  D. Ganten,et al.  Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene , 1990, Nature.

[157]  S. Lindquist,et al.  The FLP recombinase of yeast catalyzes site-specific recombination in the drosophila genome , 1989, Cell.

[158]  M. Capecchi,et al.  Altering the genome by homologous recombination. , 1989, Science.

[159]  N. Henderson,et al.  Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[160]  M. Capecchi,et al.  Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells , 1987, Cell.

[161]  M. Monk,et al.  HPRT-deficient (Lesch–Nyhan) mouse embryos derived from germline colonization by cultured cells , 1987, Nature.

[162]  A. Bradley,et al.  A potential animal model for Lesch–Nyhan syndrome through introduction of HPRT mutations into mice , 1987, Nature.

[163]  P Argos,et al.  The integrase family of site‐specific recombinases: regional similarities and global diversity. , 1986, The EMBO journal.

[164]  R. Kucherlapati,et al.  Insertion of DNA sequences into the human chromosomal β-globin locus by homologous recombination , 1985, Nature.

[165]  R Kemler,et al.  The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. , 1985, Journal of embryology and experimental morphology.

[166]  W. Anderson,et al.  Prospects for human gene therapy. , 1984, The Journal of reproductive medicine.

[167]  K. Abremski,et al.  Site-specific recombination by the bacteriophage P1 lox-Cre system. Cre-mediated synapsis of two lox sites. , 1984, Journal of molecular biology.

[168]  R. Hoess,et al.  Bacteriophage P1 site-specific recombination. Purification and properties of the Cre recombinase protein. , 1984, The Journal of biological chemistry.

[169]  R. Hoess,et al.  Studies on the properties of P1 site-specific recombination: Evidence for topologically unlinked products following recombination , 1983, Cell.

[170]  R. Hoess,et al.  P1 site-specific recombination: nucleotide sequence of the recombining sites. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[171]  G. Martin,et al.  Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[172]  N. Sternberg,et al.  Bacteriophage P1 site-specific recombination. I. Recombination between loxP sites. , 1981, Journal of molecular biology.

[173]  M. Kaufman,et al.  Establishment in culture of pluripotential cells from mouse embryos , 1981, Nature.

[174]  James R. Broach,et al.  Replication and recombination functions associated with the yeast plasmid, 2μ circle , 1980, Cell.

[175]  E. Giblett,et al.  Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. , 1972, Lancet.

[176]  G. Ackerman,et al.  A phase and electron microscopic study of vasculogenesis and erythropoiesis in the yolk sac of the mouse , 1971, The Anatomical record.

[177]  F. Gonzalez-crussi,et al.  Vasculogenesis in the chick embryo. An ultrastructural study. , 1971, The American journal of anatomy.

[178]  Y. Miura,et al.  Tissue interaction and the formation of the first erythroblasts of the chick embryo. , 1969, Developmental biology.

[179]  J. Seegmiller,et al.  Enzyme Defect Associated with a Sex-Linked Human Neurological Disorder and Excessive Purine Synthesis , 1967, Science.

[180]  F. Wilt Erythropoiesis in the Chick Embryo: The Role of Endoderm , 1965, Science.

[181]  G. Ackerman,et al.  Vasculogenesis and erythropoiesis in the living yolk sac of the chick embryo a phase microscopic study , 1961, The Anatomical record.

[182]  P. Libby Lesion versus lumen , 1995, Nature Medicine.

[183]  K. Rajewsky,et al.  A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells. , 1995, Nucleic acids research.

[184]  R. Lefkowitz,et al.  Enhanced Myocardial Function inTransgenic Mice Overexpressing theP2-Adrenergic Receptor , 1994 .

[185]  R. Ross,et al.  ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[186]  N. Maeda,et al.  Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[187]  J. Logan,et al.  An Isologous Porcine Promoter Permits High Level Expression of Human Hemoglobin in Transgenic Swine , 1994, Bio/Technology.

[188]  W. Eyestone,et al.  Challenges and progress in the production of transgenic cattle. , 1994, Reproduction, fertility, and development.

[189]  N. First,et al.  Systems for production of calves from cultured bovine embryonic cells. , 1994, Reproduction, fertility, and development.

[190]  C. Whitelaw,et al.  Chromosomal position effects and the modulation of transgene expression. , 1994, Reproduction, fertility, and development.

[191]  M. Wheeler,et al.  Development and validation of swine embryonic stem cells: a review. , 1994, Reproduction, fertility, and development.

[192]  A. Dorling,et al.  Prospects for xenografting. , 1994, Current opinion in immunology.

[193]  K. Chien,et al.  Transcriptional regulation during cardiac growth and development. , 1993, Annual review of physiology.

[194]  K. Chien,et al.  In vivo murine cardiac hypertrophy : a novel model to identify genetic signaling mechanisms that activate an adaptive physiological response , 1993 .

[195]  M. Wiles,et al.  Hematopoietic commitment during embryonic stem cell differentiation in culture. , 1993, Molecular and cellular biology.

[196]  U. Chen,et al.  Differentiation of Mouse Embryonic Stem Cells to Lympho-Hematopoietic Lineagesin Vitro , 1992, Developmental immunology.

[197]  B. Koller,et al.  Altering genes in animals by gene targeting. , 1992, Annual review of immunology.

[198]  M. Hooper Embryonal Stem Cells: Introducing Planned Changes into the Animal Germline , 1992 .

[199]  G. Anderson Isolation and use of embryonic stem cells from livestock species , 1992 .

[200]  M. Tavassoli Embryonic and fetal hemopoiesis: an overview. , 1991, Blood cells.

[201]  S. Solomon,et al.  A molecular basis for familial hypertrophic cardiomyopathy: an alpha/beta cardiac myosin heavy chain hybrid gene. , 1990, Cell.

[202]  M. Perricaudet,et al.  Evaluation of the transfer and expression in mice of an enzyme-encoding gene using a human adenovirus vector. , 1990, Human gene therapy.

[203]  R. Blaese,et al.  The ADA human gene therapy clinical protocol: Points to Consider response with clinical protocol, July 6, 1990. , 1990, Human gene therapy.

[204]  R. Hoess,et al.  The Cre-lox Recombination System , 1990 .

[205]  M. Capecchi The new mouse genetics: altering the genome by gene targeting. , 1989, Trends in genetics : TIG.

[206]  E. Robertson Pluripotential stem cell lines as a route into the mouse germ line , 1986 .

[207]  R. Palmiter,et al.  Germ-line transformation of mice. , 1986, Annual review of genetics.

[208]  F. Sabin Studies on the origin of blood vessels and of red corpuscles as seen in the living blastoderm of the chick during the second day of incubation , 1920 .