TARGETED DISRUPTION OF THE HUNTINGTONS-DISEASE GENE RESULTS IN EMBRYONIC LETHALITY AND BEHAVIORAL AND MORPHOLOGICAL-CHANGES IN HETEROZYGOTES

被引：630
作者：
NASIR, J
FLORESCO, SB
OKUSKY, JR
DIEWERT, VM
RICHMAN, JM
ZEISLER, J
BOROWSKI, A
MARTH, JD
PHILLIPS, AG
HAYDEN, MR
机构：
[1] UNIV BRITISH COLUMBIA, DEPT MED GENET, VANCOUVER, BC V6T 1Z4, CANADA
[2] UNIV BRITISH COLUMBIA, DEPT PSYCHOL, VANCOUVER, BC V6T 1Z4, CANADA
[3] UNIV BRITISH COLUMBIA, DEPT PATHOL & LAB MED, VANCOUVER, BC V6T 1Z4, CANADA
[4] UNIV BRITISH COLUMBIA, DEPT CLIN DENT SCI, VANCOUVER, BC V6T 1Z4, CANADA
[5] UNIV BRITISH COLUMBIA, BIOMED RES CTR, VANCOUVER, BC V6T 1Z4, CANADA
[6] UNIV BRITISH COLUMBIA, CTR MOLEC MED & THERAPEUT, VANCOUVER, BC V6T 1Z4, CANADA
来源：
CELL | 1995年 / 81卷 / 05期
基金：
英国医学研究理事会;
关键词：
D O I：
10.1016/0092-8674(95)90542-1
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 (Hdh(ex5)), 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 Hdh(ex5) 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.
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收藏
页码：811 / 823
页数：13
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