Murine mentors: Transgenic and knockout models of surgical disease

Annals of Surgery

Volumn 229, Issue 1, 1999, Pages 21-40

  Arbeit, Jeffrey M ^a,b   Hirose, Ryutaro ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMAL MODEL; BREAST CANCER; CANCER; CARDIOVASCULAR DISEASE; EMBRYO MORTALITY; ENTERITIS; GASTROINTESTINAL POLYPOSIS; GENE FUNCTION; GENETIC MANIPULATION; HISTOCOMPATIBILITY; KNOCKOUT GENE; KNOCKOUT MOUSE; MOUSE; NONHUMAN; PRIORITY JOURNAL; REVIEW; SKIN CANCER; TECHNIQUE; TRANSGENE; TRANSGENIC MOUSE; TRANSPLANTATION; UTERINE CERVIX CANCER; WOUND HEALING;

ANIMALS; CLINICAL LABORATORY TECHNIQUES; DISEASE MODELS, ANIMAL; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC;

EID: 0033497321     PISSN: 00034932     EISSN: None     Source Type: Journal    
DOI: 10.1097/00000658-199901000-00004     Document Type: Review

References (166)

1. Palmiter R, RL B. Germ-line transformation of mice. Ann Rev Genet 1986; 20:465-499.
2. Jaenisch R. Transgenic animals. Science 1988; 240:1468-1474.
3. Hogan B, Beddington R, Costantini F, Lacy E. Manipulating the Mouse Embryo, 2d ed. Cold Spring Harbor, NY: Cold Spring Harbor Press, 1994.
4. Mintz B, Illmensee K. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci 1975; 72:3585-3589.
5. Evans M, Kaufman M. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981; 292:154-156.
6. Thomas K, Capecchi M. Introduction of homologous DNA sequences into mammalian cells induces mutation in the cognate gene. Nature 1986; 324:34-38.
7. Kühn M, Bradley A, Robertson E, Evans M. A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature 1987; 326:295-298.
8. Thomas K, Capecchi M. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 1987; 51:502-513.
9. Alberts B, Bray D, Lewis J, et al. Molecular Biology of the Cell. New York: Garland Publishing, 1993:364.
10. Mustoe T, Pierce G, Thomason A, et al. Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science 1987; 237:1333-1336.
11. Brown R, Breeden M, Greenhalgh D. PDGF and TGF-alpha act synergistically to improve wound healing in the genetically diabetic mouse. J Surg Res 1994; 56:562-570.
12. Werner S, Smola H, Liao X, et al. The function of KGF in morphogenesis of epithelium and reepithelialization of wounds. Science 1994; 266:819-822.
13. Guo L, Degenstein L, Fuchs E. Keratinocyte growth factor is required for hair development but not for wound healing. Genes Dev 1996; 15:165-175.
14. 1-deficient mouse. Wound Rep Reg 1995; 3:25-36.
15. 1-deficient mice: identification of isoform-specific activities in vivo. J Leukoc Biol 1996; 59:769-774.
16. Vassar R, Fuchs E. Transgenic mice provide new insights into the role of TGF-a during epidermal development and differentiation. Genes Dev 1991; 5:714-722.
17. Romer J, Bugge T, Pyke C, et al. Impaired wound healing in mice with a disrupted plasminogen gene. Nature Med 1996; 2:287-292.
18. Forsberg E, Hirsch E, Fröhlich L, et al. Skin wounds and severed nerves heal normally in mice lacking tenascin-C. Proc Natl Acad Sci USA 1996; 93:6594-6599.
19. Carmeliet P. Physiological consequences of over-or underexpression of fibrinolytic system components in transgenic mice. Baillieres Clin Haematol 1995; 8:391-401.
20. Connolly A, Ishihara H, Kahn M, et al. Role of the thrombin receptor in development and evidence for a second receptor. Nature 1996; 381:516-519.
21. George E, Georges-Labouesse E, Patel-King R, et al. Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 1993; 119:1079-1091.
22. Yang J, Rayburn H, Hynes R. Embryonic mesodermal defects in a5 integrin-deficient mice. Development 1993; 119:1093-1105.
23. Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996; 380:435-439.
24. Kulkarni A, Huh C, Becker D, et al. Transforming growth factor b1 null mutation causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 1993; 90:770-774.
25. Threadgill D, Dlugosz A, Hansen L, et al. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science 1995; 269:230-234.
26. Lin M, Rockman H, Chien K. Heart and lung disease in engineered mice. Nature Med 1995; 1:749-751.
27. Chien K. Molecular medicine in genetically engineered animals. J Clin Invest 1996; 97:901-909.
28. Brannan C, Perkins A, Vogel K, et al. Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. Genes Dev 1994; 8:1019-1029.
29. Kurihara Y, Kurihara H, Oda H, et al. Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1. J Clin Invest 1995; 96:293-300.
30. Donovan M, Hahn R, Tessarollo L, Hempstead B. Identification of an essential nonneuronal function of neurotrophin 3 in mammalian cardiac development. Nature Genet 1996; 14:210-213.
31. Chisaka O, Capecchi M. Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Nature 1991; 350:473-479.
32. Jaber M, Koch W, Rockman H, et al. Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function. Proc Natl Acad Sci 1996;93:12974-12979.
33. Dryson E, Sucov H, Kubalak S, et al. Atrial-like phenotype is associated with embryonic ventricular failure in retinoid X receptor alpha-1 mice. Proc Natl Acad Sci 1995; 92:7386-7390.
34. Reaume A, de Sousa P, Kulkarni S, et al. Cardiac malformation in neonatal mice lacking connexin 43. Science 1995; 267:1831-1834.
35. Milano C, Dolber P, Rockman H, et al. Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy. Proc Natl Acad Sci USA 1994; 91: 10109-10113.
36. Hunter J, Tanaka N, Rockman H, et al. Ventricular expression of a MLC-2v-ras fusion gene induces cardiac hypertrophy and selective diastolic dysfunction in transgenic mise. J Biol Chem 1995; 270: 23173-23178.
37. Milano C, Allen L, Rockman H, et al. Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor. Science 1994; 268:1350-1353.
38. Koch W, Rockman H, Samama P, et al. Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor. Science 1995; 268:1350-1353.
39. Chien K. Cardiac muscle diseases in genetically engineered mice: evolution of molecular physiology. Am J Physiol 1995; 269:H755-766.
40. Samama P, Bond R, Rockman H, et al. Ligand-induced overexpression of a constitutively active beta 2-adrenergic receptor: pharmacological creation of a phenotype in transgenic mice. Proc Natl Acad Sci USA 1997; 94:137-141.
41. Breslow J. Transgenic mouse-models of lipoprotein metabolism and atherosclerosis. Proc Natl Acad Sci USA 1993; 90:8314-8318.
42. Warden C, Hedrick C, Qiao J, et al. Atherosclerosis in transgenic mice overexpressing apolipoprotein A-II. Science 1993; 261:469-472.
43. Shachter N, Ebara T, Ramakrishnan R, et al. Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein C1. J Clin Invest 1996; 98:846-855.
44. de Silva H, Lauer S, Wang J, et al. Overexpression of human apolipoprotein C-III in transgenic mice results in an accumulation of apolipoprotein B48 remnants that is corrected by excess apolipoprotein E. J Biol Chem 1994; 269:2324-2335.
45. Aalto-Setala K, Weinstock P, Bisgaier C, et al. Further characterization of the metabolic properties of triglyceride-rich lipoproteins from human and mouse apoC-III transgenic mice. J Lipid Res 1996; 37:1802-1811.
46. Lawn R, Wade D, Hammer R, et al. Atherogenesis in transgenic mice expressing human apolipoprotem(a). Nature 1992; 360:670-672.
47. Linton M, Farese R, Chiese G, et al. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein (a). J Clin Invest 1993; 92:3029-3037.
48. Marotti K, Castle C, Boyle T, et al. Severe atherosclerosis in transgenic mice expressing simian cholesterol ester transfer protein. Nature 1993; 364:73-75.
49. Plump A, Smith J, Hayek T, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 1992; 71:343-353.
50. Ishibashi S, Brown M, Goldstein J, et al. Hypercholesterolemia in low-density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. J Clin Invest 1993; 92:883-893.
51. Nakashima Y, Plump A, Raines E, et al. Apo E-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb 1994; 14:133-140.
52. Shimano H, Yamada N, Katsuki M, et al. Overexpression of apolipoprotein E in transgenic mice: marked reduction in plasma lipoproteins except high-density lipoprotein and resistance against diet-induced hypercholesterolemia. Proc Natl Acad Sci USA 1992: 89: 1750-1754.
53. Shimada M, Ishibashi S, Inaba T, et al. Suppression of diet-induced atherosclerosis in low-density lipoprotein receptor knockout mice overexpressing lipoprotein lipase. Proc Natl Acad Sci USA 1996; 93:7242-7246.
54. Pàszty C, Maeda N, Verstuyft J, Rubin E. Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice. J Clin Invest 1994; 94:899-903.
55. Pfeffer K, Mak T. Lymphocyte ontogeny and activation in gene targeted mutant mice. Ann Rev Immunol 1994; 12:367-411.
56. Chitilian H, Auchincloss H. Studies of transplantation immunology with major histocompatibility complex knockout mice. J Heart Lung Transplant 1997; 16:153-159.
57. Bach F, Auchincloss H, eds. Transplantation Immunology. New York: Wiley-Liss, 1995:53-86.
58. Sachs D, Sykes M, Greenstein J, Cosimi A. Tolerance and xenograft survival. Nature Med 1995; 1:969.
59. York I, Rock K. Antigen processing and presentation by the class I major histocompatibility complex. Ann Rev Immunol 1996; 14:369-396.
60. Weenink S, Gautman A. Antigen presentation by MHC class II molecules. Immunol Cell Biol 1997; 75:69-81.
61. Zijlstra M, Li E, Saijadi F, et al. Germ-line transmission of a disrupted b2-microglobulin gene produced by homologous recombination in embryonic stem cells. Nature 1989; 342:435-438.
62. Koller B, Marrack P, Kappler J, Smithies O. Normal development of mice deficient in b2m MHC class I proteins, and CD8+ T cells. Science 1990; 248:1227-1230.
63. Van Kaer L, Ashton-Rickardt P, Pleogh H, Tonegawa S. TAP-1 mutant mice are deficient in antigen presentation, surface 3 class 1 molecules, and CD4-8+ T cells. Cell 1992; 71:1205-1214.
64. Lee R, Grusby M, Laufer T, et al. CD8+ effector cells responding to residual class 1 antigens, with help from CD4+ cells stimulated indirectly, cause rejection of major histocompatibility complex-deficient skin grafts. Transplantation 1997; 63:1123-1133.
65. Osorio R, Ascher N, Jaenisch R, et al. Major histocompatibility complex class I deficiency prolongs islet allograft survival. Diabetes 1993;42:1520-1527.
66. Cosgrove D, Gray D, Dierich A, et al. Mice lacking MHC class II molecules. Cell 1991; 66:1051-1066.
67. Grusby M, Johnson R, Papaioannou V, Glimicher L. Depletion of CD4+ T cells in major histocompatibility complex II-deficient mice. Science 1991;253:1417-1423.
68. Campos L, Naji A, Deli B, et al. Survival of MHC-deficient mouse heterotopic cardiac allografts. Transplantation 1995; 59:187-191.
69. Sun H, Wakizaka Y, Rao A, et al. Use of MHC class I or II knockout mice to delineate the role of these molecules in acceptance/rejection of xenografts. Transplant Proc 1996; 28:732.
70. Fung-Leung W, Schilham M, Rahemtulla A, et al. CD8 is needed for development of cytotoxic T cells but not helper T cells. Cell 1991; 65:443-449.
71. Krieger N, Yin D, Fathman C. CD4+ but not CD8+ cells are essential for allorjection. J Exp Med 1996; 184:2013-2018.
72. Rahemtulla A, Fung-Leung W, Schilham M, et al. Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature 1991; 353:181-184.
73. Saleem S, Bogumila B, Lowry R, et al. Acute rejection of vascularized heart allografts in the absence of IFNg. Transplantation 1996; 62:1908-1911.
74. Dorling A, Riesbeck K, Warrens A, Lechler R. Clinical xenotransplantation of solid organs. Lancet 1997; 349:867-871.
75. Sandrin M, Fodor W, Mouhtouris E, et al. Enzymatic remodeling of the carbohydrate surface of a xenogenic cell substantially reduces human antibody binding and complement-mediated cytolysis. Nature Med 1995; 1:1261-1267.
76. Sharma A, Okabe J, Birch P, et al. Reduction in the level of Gal(alpha 1,3)Gal in transgenic mice and pigs by the expression of an alpha(1,2)fucosyltransferase. Proc Natl Acad Sci USA 1996; 98: 7190-7195.
77. Rosengard A, Gary N, Langford G, et al. Tissue expression of human complement inhibitor, decay-accelerating factor, in transgenic pigs. Transplantation 1995; 59:1325-1333.
78. Diamond L, McCurry K, Martin M, et al. Characterization of transgenic pigs expressing functionally active human CD59 on cardiac endothelium. Transplantation 1996; 61:1241-1249.
79. McCurry K, Kooyman D, Alvardo C, et al. Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. Nature Med 1995; 1:423-427.
80. Mandel T, Koulmanda M, Cozzi E, et al. Transplantation of normal and DAF-transgenic fetal pig pancreas into cynomolgus monkeys. Transplant Proc 1997; 29:940.
81. Sadlack B, Merz H, Schorle H, et al. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 1993; 75:253-261.
82. Kühn R, Löhler J, Rennick D, et al. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 1993; 75:263-274.
83. Mombaerts P, Mizoguchi E, Grusby M, et al. Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 1993; 75:275-282.
84. Rudolph U, Finegold M, Rich S, et al. Gi2a protein deficiency: a model for inflammatory bowel disease. J Clin Invest 1995; 15:101S-105S.
85. Hermiston M, Gordon J. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science 1995; 270:1203-1207.
86. Huang P, Dawson T, Bredt D, et al. Targeted disruption of the neuronal nitric oxide synthase gene. Cell 1993; 75:1273-1286.
87. Lane P. Association of megacolon with two recessive spotting genes in the mouse. J Hered 1966; 57:29-31.
88. Baynash A, Hosoda K, Giald A, et al. Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Cell 1994; 79:1277-1285.
89. Sánchez, M. Silos-Santiago I, Frisén J. et al. Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 1996; 382:70-73.
90. Pichel J, Shen L, Shen H, et al. Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 1996; 382:73-76.
91. Moore M, Klein R, Farinas I, et al. Renal and neuronal abnormalities in mice lacking GDNF. Nature 1996; 382:76-79.
92. Hosoda K, Hammer R, Richardson J, et al. Targeted and natural (Piebald-lethal) mutations of endothelin-b receptor gene produce megacolon associated with spotted coat color in mice. Cell 1994; 79:1267-1276.
93. Schuchardt A, Agati V, Larsson-Biomberg L, et al. Detects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 1994; 367:380-383.
94. Romeo G, Ronchetto P, Luo Y, et al. Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease. Nature 1994; 367:377-378.
95. Edery P, Lyonnet S, Mulligan L, et al. Mutations of the RET proto-oncogene in Hirschsprung's disease. Nature 1994; 367:378-380.
96. Knudson AJ. Mutation and cancer: a personal odyssey. Adv Cancer Res 1995; 67:1-23.
97. Sherr C. Cancer cell cycles. Science 1996; 274:1672-1677.
98. Meuth M. Patterns of mutation in cancer cells. Cancer Surveys 1996; 28:33-46.
99. Coletta P, Cartwright E, Markham A. Transgenic models and cancer treatment. Cancer Treat Rev 1996; 21:565-576.
100. Hanahan D. Dissecting multistep tumorigenesis in transgenic mice. Science 1988; 22:479-519.
101. Cardiff R. The biology of mammary transgenes: five rules. J Mamm Gland Biol Neopl 1996; 1:61-73.
102. Jacks T, Fazeli A, Schmitt E, et al. Effects of an Rb mutation in the mouse. Nature 1992; 359:295-300.
103. Donnehower L, Godley L, Aldaz C, et al. Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability. Genes Dev 1995; 9:882-895.
104. Jacks T, Shane Shih T, Schmitt E, et al. Tumor predisposition in mice heterozygous for a targeted mutation in Nf1. Nature Genet 1994; 7:353-361.
105. Hakem R, de la Pompa J, Sirard C, et al. The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse. Cell 1996; 85:1009-1023.
106. Sharan S, Morimatsu M, Albrecht U, et al. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature 1997; 386:804-810.
107. Hollstein M, Soussi T, Thomas G, et al. P53 gene alterations m human tumors: perspectives for cancer control. Rec Res Cancer Res 1997; 43:369-389.
108. Malkin D, Li F, Strong L, et al. Germline p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 1990; 250:1233-1238.
109. Harris C. P53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology, and cancer risk assessment. Environ Health Perspect 1996; 104(S3):435-439.
110. Donnehower L. The p53-deficient mouse: a model for basic and applied cancer studies. Sem Cancer Biol 1996; 7:269-278.
111. Lowe S, Ruley H, Jacks T, Houseman D. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 1993; 74:957-967.
112. Kinzler K, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 1996; 87:159-170.
113. Groden J, Thliveris A, Samowitz W, et al. Identification and characterization of the familial adenomatosis polyposis gene. Cell 1991; 66:589-600.
114. Lynch H, Smyrk T. Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review. Cancer 1996; 78:1149-1167.
115. Peltomaki P, de la Chapelle A. Mutations predisposing to hereditary nonpolyposis colorectal cancer. Adv Cancer Res 1997; 71:93-119.
116. Bilger A, Shoemaker A, Gould D, Dove W. Manipulation of the mouse germline in the study of Min-induced neoplasia. Sem Cancer Biol 1996; 7:249-260.
117. Prolla T, Abuin A, Bradley A. DNA mismatch repair deficient mice in cancer research. Sem Cancer Biol 1996; 7:241-247.
118. Reitmair A, Redston M, Chun Cai J, et al. Spontaneous intestinal carcinomas and skin neoplasms in Msh2-deficient mice. Cancer Res 1996; 56:3842-3849.
119. Edelmann W, Yang K, Umar A, et al. Mutation in the mismatch repair gene Msh6 causes cancer susceptibility. Cell 1997; 91:467-477.
120. Oshima M, Oshima H, Kitagawa K, et al. Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene. Proc Natl Acad Sci USA 1995; 92:4482-4486.
121. Fodde R, Edelmann W, Yang K, et al. A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proc Natl Acad Sci USA 1994; 91:8969-8973.
122. Moser A, Shoemaker A, Connelly C, et al. Homozygosity for the Min allele of Apc results in disruption of mouse development prior to gastrulation. Developmental Dynamics 1995; 203:422-433.
123. Shibata H, Toyama K, Shioya H, et al. Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science 1997; 278:120-123.
124. Boolbol S, Dannenberg A, Chadburn A, et al. Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial polyposis. Cancer Res 1996; 56:2556-2560.
125. Jacoby R, Marshall D, Newton M, et al. Chemoprevention of spontaneous intestinal adenomas in the ApcMin mouse model by the nonsteroidal anti-inflammatory drug piroxicam. Cancer Res 1996; 56:710-714.
126. Oshima M, Dinchuk J, Kargman S, et al. Suppression of intestinal polyposis in ApcD716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996; 87:803-809.
127. Webster M, Muller W. Mammary tumorigenesis and metastasis in transgenic mice. Sem Cancer Biol 1994; 5:69-76.
128. Guy C, Webster M, Schaller M, et al. Expression of the c-neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci USA 1992; 89:10578-10582.
129. Stewart T, Pattengale P, Leder P. Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell 1984; 38(3):627-637.
130. Matsui Y, Halter S, Holt J, et al. Development of mammary hyperplasia and neoplasia in MMTV-TGF-alpha transgenic mice. Cell 1990; 61(6):1147-1155.
131. Sinn E, Muller W, Pattengale P, et al. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell 1987; 49:465-495.
132. Wang T, Cardiff R, Zukerberg L, et al. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 1994; 369(6482):669-671.
133. Tsukamoto A, Grosschedl R, Guzman R, et al. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell 1988; 55(4):619-625.
134. Jhappan C, Gallahan D, Stahle C, et al. Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev 1992; 6(3):345-355.
135. Wolman S, Heppner G, Wolman E. New directions in breast cancer research. FASEB J 1997; 11:535-543.
136. Arbeit J. Transgenic models of epidermal neoplasia and multistage carcinogenesis. Cancer Surveys 1996; 26:7-34.
137. Greenhalgh D, Rothnagel J, Quintanilla M, et al. Induction of epidermal hyperplasia, hyperkeratosis, and papillomas in transgenic mice by targeted v-Ha-ras oncogene. Molecular Carcinogenesis 1993; 7:99-110.
138. Greenhalgh D, Rothnagel J, Wang X-J, et al. Hyperplasia, hyperkeratosis and benign tumor production in transgenic mice by a targeted v-fos oncogene suggest a role for fos in epidermal differentiation and neoplasia. Oncogene 1993; 8:2145-2157.
139. Greenhalgh D, Quintanilla M, Orengo C, et al. Cooperation between v-fos and v-rasHA induces autonomous papillomas in transgenic epidermis but not malignant conversion. Cancer Res 1993; 53:5071-5075.
140. Leder A, Kuo A, Cardiff R, et al. v-Ha-ras transgene abrogates the initiation step in mouse skin tumorigenesis: effects of phorbol esters and retinoic acid. Proc Natl Acad Sci USA 1990; 87:9178-9182.
141. Coussens L, Hanahan D, Arbeit J. Genetic susceptibility, alterations in differentiation, and invasion during multistage squamous carcinogenesis in K14-HPV16 transgenic mice. Am J Pathol 1996; 149: 1899-1917.
142. Arbeit J, Oison D, Hanahan D. Upregulation of fibroblast growth factors and their receptors during multistage epidermal carcinogenesis in K14-HPV16 transgenic mice. Oncogene 1996; 13:1847-1857.
143. Hurlin P, Foley K, Ayer D, et al. Myc and mad are inversely regulated during epidermal differentiation and HPV-associated tumorigenesis. Oncogene 1995; 11:2487-2501.
144. Chin L, Pomerantz J, Polsky D, et al. Cooperative effects of INK4a and ras in melanoma susceptibility in vivo. Gene Dev 1997; 11: 2822-2834.
145. Takayama H, LaRochelle W, Sharp R, et al. Diverse tumorigenesis associated with aberrant development in mice overexpressmg hepatocyte growth factor/scatter factor. Proc Natl Acad Sci USA 1997; 94:701-706.
146. Bradl M, Klein-Szanto A, Porter S, Mintz B. Malignant melanoma in transgenic mice. Proc Natl Acad Sci USA 1991; 88:164-168.
147. Iwamoto T, Takahashi M, Ito M, et al. Aberrant melanogenesis and melanocytic tumor development in transgenic mice that carry a metallothionein/ret fusion gene. EMBO J 1991; 10:3167-3175.
148. Arbeit J, Howley P, Hanahan D. Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in HPV16 transgenic mice. Proc Natl Acad Sci USA 1996; 93:2930-2935.
149. Chisari F. Analysis of hepdnavirus gene expression, biology, and pathogenesis in the transgenic mouse. Curr Topic Microbiol Immunol 1991; 168:85-101
150. Kim C, Koike K, Saito I, et al. Hbx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 1991; 351:317-320.
151. Vogel J, Hinrichs S, Napolitano L, et al. Liver cancer in transgenic mic carrying the human immunodeficiency virus tat gene. Cancer Res 1991: 51:6686-6690.
152. Dubois N, Bennoun M. Allemand I. et al. Time-course development of differentiated hepatocarcinoma and lung metastasis in transgenic mice. J Hepatol 1991; 13:227-239.
153. Chisari F, Klopchin K, Moriyama T, et al. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell 1989; 59:1145-1156.
154. Christofori G, Hanahan D. Molecular dissection of multistage tumorigenesis in transgenic mice. Sem Cancer Biol 1994; 5:3-12.
155. Parangi S, O'Reilly M, Christofori G, et al. Antiangiogenic therapy of transgenic mice impairs de novo tumor growth. Proc Natl Acad Sci USA 1996; 93:2002-2007.
156. Lacey M, Alpert S, Hanahan D. Bovine papillomavirus genome elicits skin tumors in transgenic mice. Nature 1986; 323:609-612.
157. Schuh A, Keating S, Monteclaro F, et al. Obligatory wounding requirements for tumorigenesis in v-jun transgenic mice. Nature 1990; 346:756-760.
158. Furth P, St. Onge L, Boger H, et al. Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. Proc Natl Acad Sci USA 1994; 92:9302-9306.
159. Kistner A, Gossen M, Zimmermann F, et al. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci USA 1996; 93:10933-10938.
160. Wang Y, DeMayo F, Tsai S, O'Malley B. Ligand-inducible and liver-specific target gene expression in transgenic mice. Nature 1997; 15:239-243.
161. No D, Yao T, Evans R. Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc Natl Acad Sci USA 1996; 93:3346-3351.
162. Baron U, Gossen M, Bujard H. Tetracycline-controlled transcription in eukaryotes: novel transactivators with graded transactivation potential. Nucleic Acids Res 1997; 25:2723-2729.
163. Akagi K, Sandig V, Vooijs M, et al. Cre-mediated somatic site-specific recombination in mice. Nucleic Acids Res 1997; 25:1766-1773.
164. Rajewsky K, Gu H, Kuhn R, et al. Conditional gene targeting. J Clin Invest 1996; 98:600-603.
165. St Onge L, Furth P, Gruss P. Temporal control of the Cre recombinase in transgenic mice by a tetracycline-responsive promoter. Nucleic Acids Res 1996; 24:3875-3877.
166. Feil R, Brocard J, Mascrez B, et al. Ligand-activated site-specific recombination in mice. Proc Natl Acad Sci USA 1996; 93:10887-10890.