A Novel mouse model of enhanced proteostasis: Full-length human heat shock factor 1 transgenic mice

Anson Pierce, Rochelle Wei, Dipti Halade, Si Eun Yoo, Qitao Ran, Arlan Richardson

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The heat shock response (HSR) is controlled by the master transcriptional regulator heat shock factor 1 (HSF1). HSF1 maintains proteostasis and resistance to stress through production of heat shock proteins (HSPs). No transgenic model exists that overexpresses HSF1 in tissues of the central nervous system (CNS). We generated a transgenic mouse overexpressing full-length non-mutant HSF1 and observed a 2-4-fold increase in HSF1 mRNA and protein expression in all tissues studied of HSF1 transgenic (HSF1+/0) mice compared to wild type (WT) littermates, including several regions of the CNS. Basal expression of HSP70 and 90 showed only mild tissue-specific changes; however, in response to forced exercise, the skeletal muscle HSR was more elevated in HSF1+/0 mice compared to WT littermates and in fibroblasts following heat shock, as indicated by levels of inducible HSP70 mRNA and protein. HSF1+/0 cells elicited a significantly more robust HSR in response to expression of the 82 repeat polyglutamine-YFP fusion construct (Q82YFP) and maintained proteasome-dependent processing of Q82YFP compared to WT fibroblasts. Overexpression of HSF1 was associated with fewer, but larger Q82YFP aggregates resembling aggresomes in HSF1+/0 cells, and increased viability. Therefore, our data demonstrate that tissues and cells from mice overexpressing full-length non-mutant HSF1 exhibit enhanced proteostasis.

Original languageEnglish (US)
Pages (from-to)59-65
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume402
Issue number1
DOIs
StatePublished - Nov 5 2010

Keywords

  • Aggresome
  • Chaperones
  • Heat shock proteins
  • Heat shock response
  • Heat shock transcription factor 1
  • Polyglutamine

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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