Overexpression of heat shock protein 70 in R6/2 Huntington's disease mice has only modest effects on disease progression.
Author
Summary, in English
Huntington’s disease (HD) is a neurodegenerative disorder caused by expansion of a polyglutamine tract in a protein called huntingtin. The inducible form of heat shock protein 70 (Hsp70) has been shown to reduce polyglutamine-induced toxicity. To investigate if overexpression of Hsp70 can affect disease progression in a mouse model of HD, we crossed R6/2 mice, expressing exon 1 of the HD gene with an expanded CAG repeat, with mice overexpressing Hsp70 (both types of transgenic mice were of the CBAxC57BL/6 strain). The resulting R6/2-Hsp70 transgenics exhibited 5- to 15-fold increases in Hsp70 expression in neocortical, hippocampal and basal ganglia regions. This correlated with a delayed loss of body weight compared to R6/2 mice. However, the number or size of nuclear inclusions, the loss of brain weight, reduction of striatal volume, reduction in size of striatal projection neurons, downregulation of DARPP-32, development of paw clasping phenotype and early death of the mice were not affected by Hsp70 overexpression. Interestingly, the polyglutamine protein affected the potential rescuing agent, because in older R6/2-Hsp70 mice a large proportion of the Hsp70 protein was sequestrated in nuclear inclusions.
Department/s
Publishing year
2003
Language
English
Pages
47-57
Publication/Series
Brain Research
Volume
970
Issue
1-2
Links
Document type
Journal article
Publisher
Elsevier
Topic
- Neurosciences
Keywords
- Heat shock protein 70 (Hsp70)
- Inclusion
- Huntington’s disease
- Chaperone
- Transgenic
- Mouse
Status
Published
ISBN/ISSN/Other
- ISSN: 1872-6240