Caudal regression in adrenocortical dysplasia (acd) mice is caused by telomere dysfunction with subsequent p53-dependent apoptosis.

ABSTRACT: Adrenocortical dysplasia (acd) is a spontaneous autosomal recessive mouse mutation that exhibits a pleiotropic phenotype with perinatal lethality. Mutant acd embryos have caudal truncation, vertebral segmentation defects, hydronephrosis, and limb hypoplasia, resembling humans with Caudal Regression syndrome. Acd encodes Tpp1, a component of the shelterin complex that maintains telomere integrity, and consequently acd mutant mice have telomere dysfunction and genomic instability. While the association between genomic instability and cancer is well documented, the association between genomic instability and birth defects is unexplored. To determine the relationship between telomere dysfunction and embryonic malformations, we investigated mechanisms leading to the caudal dysgenesis phenotype

SUBMITTER: Vlangos CN 

PROVIDER: S-EPMC3298753 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature