Overexpression of heat shock protein 70 in R6/2 Huntington's disease mice has only modest effects on disease progression.
(2003) In Brain Research 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/113260
- author
- Hansson, Oskar ; Nylandsted, Jesper ; Castilho, Roger F ; Leist, Marcel ; Jäättelä, Marja and Brundin, Patrik LU
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Heat shock protein 70 (Hsp70), Inclusion, Huntington’s disease, Chaperone, Transgenic, Mouse
- in
- Brain Research
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041)
- 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
- 2016-04-01 11:38:29
- date last changed
- 2022-03-20 08:49:40
@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}}, keywords = {{Heat shock protein 70 (Hsp70); Inclusion; Huntington’s disease; Chaperone; Transgenic; Mouse}}, language = {{eng}}, number = {{1-2}}, pages = {{47--57}}, publisher = {{Elsevier}}, series = {{Brain Research}}, 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}}, doi = {{10.1016/S0006-8993(02)04275-0}}, volume = {{970}}, year = {{2003}}, }