Article ID Journal Published Year Pages File Type
3055891 Experimental Neurology 2011 10 Pages PDF
Abstract

The discovery of the gene mutation responsible for Huntington's disease (HD), huntingtin, in 1993 allowed for a better understanding of the pathology of and enabled the development of animal models. HD is caused by the expansion of a polyglutamine repeat region in the N-terminal of the huntingtin protein. Here we examine the behavioral, transcriptional, histopathological and anatomical characteristics of a knock-in HD mouse model with a 140 polyglutamine expansion in the huntingtin protein. This CAG 140 model contains a portion of the human exon 1 with 140 CAG repeats knocked into the mouse huntingtin gene. We have longitudinally examined the rearing behavior, accelerating rotarod, constant speed rotarod and gait for age-matched heterozygote, homozygote and non-transgenic mice and have found a significant difference in the afflicted mice. However, while there were significant differences between the non-transgenic and the knock-in mice, these behaviors were not progressive. As in HD, we show that the CAG 140 mice also have a significant decrease in striatally enriched mRNA transcripts. In addition, striatal neuronal intranuclear inclusion density increases with age. Lastly these CAG 140 mice show slight cortical thinning compared to non-transgenic mice, similarly to the cortical thinning recently reported in HD.

Research Highlights► Longitudinal behavioral analysis of CAG 140 HD mice reveals a rearing deficit. ► Accelerating rotarod deficits appear at about 11 months of age in CAG 140 mice. ► Striatal specific transcripts decline progressively starting at 6 months of age. ► NIIs appear at 6 months and progressively become more dense over time. ► The cerebral cortex of the CAG 140 mouse thins earlier than in non-transgenic mice.

Related Topics
Life Sciences Neuroscience Neurology
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