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Overexpression of heat shock protein 70 in R6/2 Huntington's disease mice has only modest effects on disease progression.

Hansson, Oskar; Nylandsted, Jesper; Castilho, Roger F; Leist, Marcel; Jäättelä, Marja and Brundin, Patrik LU (2003) In Brain Research1966-01-01+01:00 970(1-2). p.47-57
Abstract
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,... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Heat shock protein 70 (Hsp70), Inclusion, Huntington’s disease, Chaperone, Transgenic, Mouse
in
Brain Research1966-01-01+01:00
volume
970
issue
1-2
pages
47 - 57
publisher
Elsevier
external identifiers
  • wos:000182790200005
  • pmid:12706247
  • scopus:0347928859
ISSN
1872-6240
DOI
10.1016/S0006-8993(02)04275-0
language
English
LU publication?
yes
id
228e7acf-e4d2-4fd6-8745-2c1cdf9dcd4e (old id 113260)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12706247&dopt=Abstract
date added to LUP
2007-07-12 15:49:26
date last changed
2018-07-01 03:26:33
@article{228e7acf-e4d2-4fd6-8745-2c1cdf9dcd4e,
  abstract     = {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.},
  author       = {Hansson, Oskar and Nylandsted, Jesper and Castilho, Roger F and Leist, Marcel and Jäättelä, Marja and Brundin, Patrik},
  issn         = {1872-6240},
  keyword      = {Heat shock protein 70 (Hsp70),Inclusion,Huntington’s disease,Chaperone,Transgenic,Mouse},
  language     = {eng},
  number       = {1-2},
  pages        = {47--57},
  publisher    = {Elsevier},
  series       = {Brain Research1966-01-01+01:00},
  title        = {Overexpression of heat shock protein 70 in R6/2 Huntington's disease mice has only modest effects on disease progression.},
  url          = {http://dx.doi.org/10.1016/S0006-8993(02)04275-0},
  volume       = {970},
  year         = {2003},
}