Animal models of tumor-suppressor genes

Annual Review of Genetics

Volumn 35, Issue , 2001, Pages 209-241

  Hakem, R ^a   Mak, T W ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Animal models; Cancer; Gene targeting; Tumor suppressor

Indexed keywords

ATM PROTEIN; BRCA1 PROTEIN; BRCA2 PROTEIN; LONG ACTING THYROID STIMULATOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN P53;

ANIMAL MODEL; APOPTOSIS; CANCER GENETICS; CELL CYCLE; CELL DIFFERENTIATION; CELL PROLIFERATION; GENE LOCUS; GENE MUTATION; GENE TARGETING; GENOME; HETEROZYGOSITY LOSS; HUMAN; MOUSE; NEUROFIBROMATOSIS; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE; VON HIPPEL LINDAU DISEASE;

ANIMALS; APOPTOSIS; CELL CYCLE; DNA DAMAGE; DNA REPAIR; GENES, TUMOR SUPPRESSOR; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; MODELS, ANIMAL; MUTATION; NEOPLASMS, EXPERIMENTAL;

ANIMALIA;

EID: 0035679209     PISSN: 00664197     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.genet.35.102401.090432     Document Type: Review

References (182)

1. The cellular effects of E2F overexpression
2. Deficiency of retinoblastoma protein leads to inappropriate S-phase entry, activation of E2F-responsive genes, and apoptosis
3. High-frequency developmental abnormalities in p53-deficient mice
4. Atm selectively regulates distinct p53-dependent cell-cycle checkpoint and apoptotic pathways
5. Atm-deficient mice: A paradigm of ataxia telangiectasia
6. Partial rescue of the prophase I defects of Atm-deficient mice by p53 and p21 null alleles
7. p14ARF links the tumour suppressors RB and p53
8. Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome
9. Expression of a retinoblastoma transgene results in dwarf mice
10. Nfl and Gmcsf interact in myeloid leukemogenesis
11. Synergy between a human c-myc transgene and p53 null genotype in murine thymic lymphomas: Contrasting effects of homozygous and heterozygous p53 loss
12. Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues
13. A human Cds 1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage
14. ATR disruption leads to chromosomal fragmentation and early embryonic lethality
15. Apafl (CED-4 homolog) regulates programmed cell death in mammalian development
16. Cooperative effects of genes controlling the G(2)/M checkpoint
17. Human BRCA1 gene rescues the embryonic lethality of Brcal mutant mice
18. p53 transcriptional activity is essential for p53-dependent apoptosis following DNA damage
19. Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells
20. Cooperative effects of INK4a and ras in melanoma susceptibility in vivo
21. NFl tumor suppressor gene function: Narrowing the GAP
22. Mouse models of tumor development in neurofibromatosis type 1
23. Requirement for a functional Rb1 gene in murine development
24. Thymocyte apoptosis induced by p53-dependent and independent pathways
25. Shared role of the pRB-related p130 and p107 proteins in limb development
26. Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation
27. A p53-dependent mouse spindle checkpoint
28. Ablation of the retinoblastoma gene family deregulates G(1) control causing immortalization and increased cell turnover under growth-restricting conditions
29. Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice
30. Towards a unified model of tumor suppression: Lessons learned from the human patched gene
31. Roles of BRCA1 and its interacting proteins
32. Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse
33. Impaired Fas response and autoimmunity in Pten +/- mice
34. Pten is essential for embryonic development and tumour suppression
35. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
36. Pleiotropic defects in ataxia-telangiectasia protein-deficient mice
37. The murine gene p27Kipl is haplo-insufficient for tumour suppression
38. A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors
39. Muir-Torre-like syndrome in Fhit-deficient mice
40. CDK inhibitors p 18(INK4c) and p27(Kip 1) mediate two separate pathways to collaboratively suppress pituitary tumorigenesis
41. Thymic lymphomas in mice with a truncating mutation in Brca2
42. Schwann cell hyperplasia and tumors in transgenic mice expressing a naturally occurring mutant NF2 protein
43. Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2
44. Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice
45. Altered neural cell fates and medulloblastoma in mouse patched mutants
46. BRCA1 required for transcription-coupled repair of oxidative DNA damage
47. Brcal deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities
48. Merlin: The neurofibromatosis 2 tumor suppressor
49. Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor
50. Partial rescue of Brcal (5-6) early embryonic lethality by p53 or p21 null mutation
51. Developmental studies of Brcal and Brca2 knock-out mice
52. The tumor suppressor gene Brcal is required for embryonic cellular proliferation in the mouse
53. Tumorigenesis in the multiple intestinal neoplasia mouse: Redundancy of negative regulators and specificity of modifiers
54. The Rb/E2F pathway: Expanding roles and emerging paradigms
55. DNA mismatch repair and genetic instability
56. Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice
57. In vitro growth characteristics of embryo fibroblasts isolated from p53-deficient mice
58. Mice deficient in both p53 and Rb develop tumors primarily of endocrine origin
59. The Wilms tumor suppressor gene wt 1 is required for development of the spleen
60. DNA damage-induced activation of p53 by the checkpoint kinase Chk2
61. Genomic instability in Gadd45a-deficient mice
62. The role of the FHIT/FRA3B locus in cancer
63. Induction of ARF tumor suppressor gene expression and cell cycle arrest by transcription factor DMP1
64. Role for the p53 homologue p73 in E2F- 1-induced apoptosis
65. Effects of an Rb mutation in the mouse
66. Tumor spectrum analysis in p53-mutant mice
67. Tumour predisposition in mice heterozygous for a targeted mutation in Nf1
68. Senescence bypass screen identifies TBX2 which represses Cdkn2a (pl9(ARF)) and is amplified in a subset of human breast cancers
69. The oncogene and Polycomb-group gene bmi1 regulates cell proliferation and senescence through the ink4a locus
70. A transactivation-deficient mouse model provides insights into Trp53 regulation and function
71. The VHL tumour-suppressor gene paradigm
72. Tumor spectrum in ARF-deficient mice
73. Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2
74. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product pl9ARF
75. p53-deficient mice are extremely susceptible to radiation-induced tumorigenesis
76. Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage
77. Cancer-susceptibility genes. Gatekeepers and caretakers
78. Chasing the cancer demon
79. WT-1 is required for early kidney development
80. Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice. A model for Li-Fraumeni syndrome
81. Gene replacement with the human BRCA1 locus: Tissue specific expression and rescue of embryonic lethality in mice
82. Limited overlapping roles of P15(INK4b) and P18(INK4c) cell cycle inhibitors in proliferation and tumorigenesis
83. p53 transgenic mice: Accelerated erythroleukemia induction by Friend virus
84. High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene
85. Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis
86. Targeted disruption of p107: Functional overlap between p107 and Rb
87. The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin
88. Transcriptional repression of the D-type cyclin-dependent kinase inhibitor pl6 by the retinoblastoma susceptibility gene product pRb
89. Critical role for Atm in suppressing V(D)J recombination-driven thymic lymphoma
90. A common E2F-1 and p73 pathway mediates cell death induced by TCR activation
91. WT1: What has the last decade told us?
92. Inactivation of the mouse Brcal gene leads to failure in the morphogenesis of the egg cylinder in early postimplantation development
93. High metastatic potential in mice inheriting a targeted p53 missense mutation
94. p53 is required for radiation-induced apoptosis in mouse thymocytes
95. Targeted mutations of breast cancer susceptibility gene homologs in mice: Lethal phenotypes of Brcal, Brca2, Brcal/Brca2, Brcal/p53, and Brca2/p53 nullizygous embryos
96. Cancer predisposition caused by elevated mitotic recombination in Bloom mice
97. Developmental rescue of an embryoniclethal mutation in the retinoblastoma gene in chimeric mice
98. Twist is a potential oncogene that inhibits apoptosis
99. Brcal is required for T cell lineage development but not TCR loci rearrangement
100. p53 and the Li-Fraumeni syndrome
101. Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum
102. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors
103. The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation
104. p63 is a p53 homologue required for limb and epidermal morphogenesis
105. YAC complementation shows a requirement for Wt1 in the development of epicardium, adrenal gland and throughout nephrogenesis
106. p53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens
107. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse
108. Homozygosity for the Min allele of Apc results in disruption of mouse development prior to gastrulation
109. Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein
110. Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence
111. Involvement of the Ink4a gene (p16 and p 19arf) in murine tumorigenesis
112. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2)
113. Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene
114. Neurofibromatosis type 1
115. Involvement of Brca2 in DNA repair
116. Recombinase-activating gene (RAG) 2-mediated V(D)J recombination is not essential for tumorigenesis in Atm-deficient mice
117. Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems
118. Wnt signaling and cancer
119. The Ink4a tumor suppressor gene product, p19Aff, interacts with MDM2 and neutralizes MDM2's inhibition of p53
120. An anti-apoptotic role for the p53 family member, p73, during developmental neuron death
121. Tumour incidence, spectrum and ploidy in mice with a large deletion in the p53 gene
122. The genetics of breast cancer susceptibility
123. MSH2 deficiency contributes to accelerated APC-mediated intestinal tumorigenesis
124. p107 is a suppressor of retinoblastoma development in pRb-deficient mice
125. Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1
126. The p16INK4a/CDKN2A tumor suppressor and its relatives
127. Targeted disruption of the three Rb-related genes leads to loss of G(1) control and immortalization
128. A subset of p53-deficient embryos exhibit exencephaly
129. Mantle cell lymphoma is characterized by inactivation of the ATM gene
130. Spontaneous DNA damage, genome instability, and cancer - When DNA replication escapes control
131. In search of the tumour-suppressor functions of BRCA1 and BRCA2
132. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4
133. Role of the INK4a locus in tumor suppression and cell mortality
134. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2
135. A targeted disruption of the murine Brcal gene causes gammairradiation hypersensitivity and genetic instability
136. The Pezcoller lecture: Cancer cell cycles revisited
137. Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene
138. ATM and ATR: Networking cellular responses to DNA damage
139. Mlhl deficiency enhances several phenotypes of Apc(Min)/+ mice
140. A mouse model for the learning and memory deficits associated with neurofibromatosis type I
141. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo
142. Apc1638T: A mouse model delineating critical domains of the adenomatous polyposis coli protein involved in tumorigenesis and development
143. Apc1638N: A mouse model for familial adenomatous polyposis-associated desmoid tumors and cutaneous cysts
144. Inactivation of the apoptosis effector Apaf-1 in malignant melanoma
145. Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction
146. Modulation of cellular apoptotic potential: Contributions to oncogenesis
147. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
148. High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in pten+/- mice
149. Role of the p53-homologue p73 in E2Fl-induced apoptosis
150. Biallelic mutations in the ATM gene in T-prolymphocytic leukemia
151. The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2
152. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene
153. PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway
154. Brca2 is required for embryonic cellular proliferation in the mouse
155. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice
156. T cell specific loss of Pten leads to defects in central and peripheral tolerance
157. Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes
158. Differential expression and cell cycle regulation of the cyclin-dependent kinase 4 inhibitor p16Ink4
159. Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity
160. Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN
161. Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress
162. Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos
163. Enhanced proliferative potential in culture of cells from p53-deficient mice
164. Absence of Brca2 causes genome instability by chromosome breakage and loss associated with centrosome amplification
165. Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apol, and DR3 and is lethal prenatally
166. Mouse tumor model for neurofibromatosis type 1
167. Surfing the p53 network
168. Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia
169. atm and p53 cooperate in apoptosis and suppression of tumorigenesis, but not in resistance to acute radiation toxicity
170. Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched
171. The normal patched allele is expressed in medulloblastomas from mice with heterozygous germ-line mutation of patched
172. Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences
173. Conditional mutation of Brcal in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation
174. Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma
175. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development
176. p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours
177. The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice
178. Apaf1 is required for mitochondrial pathways of apoptosis and brain development
179. Gross chromosomal rearrangements and genetic exchange between nonhomologous chromosomes following BRCA2 inactivation
180. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways
181. Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization