Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes.

Abstract:

:Huntington's disease (HD) is an incurable neuropsychiatric disease associated with CAG repeat expansion within a widely expressed gene that causes selective neuronal death. To understand its normal function, we have created a targeted disruption in exon 5 of Hdh (Hdhex5), the murine homolog of the HD gene. Homozygotes die before embryonic day 8.5, initiate gastrulation, but do not proceed to the formation of somites or to organogenesis. Mice heterozygous for the Hdhex5 mutation display increased motor activity and cognitive deficits. Neuropathological assessment of two heterozygous mice shows significant neuronal loss in the subthalamic nucleus. These studies show that the HD gene is essential for postimplantation development and that it may play an important role in normal functioning of the basal ganglia.

journal_name

Cell

journal_title

Cell

authors

Nasir J,Floresco SB,O'Kusky JR,Diewert VM,Richman JM,Zeisler J,Borowski A,Marth JD,Phillips AG,Hayden MR

doi

10.1016/0092-8674(95)90542-1

subject

Has Abstract

pub_date

1995-06-02 00:00:00

pages

811-23

issue

5

eissn

0092-8674

issn

1097-4172

pii

0092-8674(95)90542-1

journal_volume

81

pub_type

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