Abstract
Telomere dysfunction and shortening induce chromosomal instability and tumorigenesis. In this study, we analyze the adrenocortical dysplasia (acd) mouse, harboring a mutation in Tpp1/Acd. Additional loss of p53 dramatically rescues the acd phenotype in an organ-specific manner, including skin hyperpigmentation and adrenal morphology, but not germ cell atrophy. Survival to weaning age is significantly increased in Acd(acd/acd) p53(-/-) mice. On the contrary, p53(-/-) and p53(+/-) mice with the Acd(acd/acd) genotype show a decreased tumor-free survival, compared with Acd(+/+) mice. Tumors from Acd(acd/acd) p53(+/-) mice show a striking switch from the classic spectrum of p53(-/-) mice toward carcinomas. The acd mouse model provides further support for an in vivo role of telomere deprotection in tumorigenesis.
MeSH terms
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Adrenal Cortex / abnormalities*
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Adrenal Cortex / metabolism
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Animals
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Carcinoma / metabolism
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Carcinoma / pathology
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism*
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Cell Transformation, Neoplastic / pathology
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Chromosomal Instability / genetics
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Chromosomal Instability / physiology
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Female
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Lymphoma / metabolism
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Lymphoma / pathology
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Male
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Mice
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Mice, Transgenic
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Organ Specificity
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Phenotype
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Sarcoma / metabolism
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Sarcoma / pathology
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Skin Neoplasms / metabolism
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Skin Neoplasms / pathology
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Skin Pigmentation / genetics
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Skin Pigmentation / physiology
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Spermatogenesis / genetics
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Spermatogenesis / physiology
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Telomere / genetics
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Telomere / physiology
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Telomere-Binding Proteins / genetics
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Telomere-Binding Proteins / physiology*
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Testis / pathology
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Testis / physiopathology
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / physiology*
Substances
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Acd protein, mouse
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Telomere-Binding Proteins
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Tumor Suppressor Protein p53