Genetic p53 deficiency partially rescues the adrenocortical dysplasia phenotype at the expense of increased tumorigenesis.
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.
Else
Tobias
T
Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109-2200, USA.
Trovato
Alessia
A
Kim
Alex C
AC
Wu
Yipin
Y
Ferguson
David O
DO
Kuick
Rork D
RD
Lucas
Peter C
PC
Hammer
Gary D
GD
D000302:Adrenal Cortex / Q000002:abnormalities* / Q000378:metabolism; D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D043171:Chromosomal Instability / Q000235:genetics / Q000502:physiology; D005260:Female; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010641:Phenotype; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D012880:Skin Pigmentation / Q000235:genetics / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D016615:Telomere / Q000235:genetics / Q000502:physiology; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000502:physiology*; D013737:Testis / Q000473:pathology / Q000503:physiopathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
C544060:Acd protein, mouse; D034501:Telomere-Binding Proteins; D016159:Tumor Suppressor Protein p53