Postnatal and adult consequences of loss of huntingtin during development: Implications for Huntington's disease.

ABSTRACT: The mutation in huntingtin (mHtt) leads to a spectrum of impairments in the developing forebrain of Huntington's disease (HD) mouse models. Whether these developmental alterations are due to loss- or gain-of-function mechanisms and contribute to HD pathogenesis is unknown. We examined the role of selective loss of huntingtin (Htt) function during development on postnatal vulnerability to cell death. We employed mice expressing very low levels of Htt throughout embryonic life to postnatal day 21 (Hdh^d•hyp). We demonstrated that Hdh^d•hyp mice exhibit: (1) late-life striatal and cortical neuronal degeneration; (2) neurological and skeletal muscle alterations; and (3) white matter tract impairments and axonal degeneration. Hdh^d•hyp embryos also exhibited subpal

SUBMITTER: Arteaga-Bracho EE 

PROVIDER: S-EPMC5102778 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature