Antagonistic pleiotropy in mice carrying a CAG repeat expansion in the range causing Huntington's disease.

ABSTRACT: Antagonist pleiotropy, where a gene exerts a beneficial effect at early stages and a deleterious effect later on in an animal's life, may explain the evolutionary persistence of devastating genetic diseases such as Huntington's disease (HD). To date, however, there is little direct experimental evidence to support this theory. Here, we studied a transgenic mouse carrying the HD mutation with a repeat of 50 CAGs (R6/2_50) that is within the pathological range of repeats causing adult-onset disease in humans. R6/2_50 mice develop characteristic HD brain aggregate pathology, with aggregates appearing predominantly in the striatum and cortex. However, they show few signs of disease in their lifetime. On the contrary, R6/2_50 mice appear to benefit from carrying the mutation. They have extended

SUBMITTER: Morton AJ 

PROVIDER: S-EPMC6328633 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature