Overexpression of the Hspa13 (Stch) gene reduces prion disease incubation time in mice

Grizenkova J.; Akhtar S.; Hummerich H.Tomlinson A.Asante E.A.Wenborn A.Fizet J.Poulter M.Wiseman F.K.Fisher E.M.C.Tybulewicz V.L.J.Brandner S.Collinge J.Lloyd S.E.

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Overexpression of the Hspa13 (Stch) gene reduces prion disease incubation time in mice

机译：Overexpression of the Hspa13 (Stch) gene reduces prion disease incubation time in mice

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Prion diseases are fatal neurodegenerative disorders that include bovine spongiform encephalopathy (BSE) and scrapie in animals and Creutzfeldt-Jakob disease (CJD) in humans. They are characterized by long incubation periods, variation in which is determined by many factors including genetic background. In some cases it is possible that incubation time may be directly correlated to the level of gene expression. To test this hypothesis, we combined incubation time data from five different inbred lines of mice with quantitative gene expression profiling in normal brains and identified five genes with expression levels that correlate with incubation time. One of these genes, Hspa13 (Stch), is a member of the Hsp70 family of ATPase heat shock proteins, which have been previously implicated in prion propagation. To test whether Hspa13 plays a causal role in determining the incubation period, we tested two overexpressing mouse models. The Tc1 human chromosome 21 (Hsa21) transchromosomic mouse model of Down syndrome is trisomic for many Hsa21 genes including Hspa13 and following Chandler/Rocky Mountain Laboratory (RML) prion inoculation, shows a 4 reduction in incubation time. Furthermore, a transgenic model with eightfold overexpression of mouse Hspa13 exhibited highly significant reductions in incubation time of 16, 15, and 7 following infection with Chandler/RML, ME7, and MRC2 prion strains, respectively. These data further implicate Hsp70-like molecular chaperones in protein misfolding disorders such as prion disease.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2012年第34期|13722-13727|共6页
作者
Grizenkova J.; Akhtar S.; Hummerich H.Tomlinson A.Asante E.A.Wenborn A.Fizet J.Poulter M.Wiseman F.K.Fisher E.M.C.Tybulewicz V.L.J.Brandner S.Collinge J.Lloyd S.E.;
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作者单位

Medical Research Council (MRC) Prion Unit, University College London (UCL) Institute of Neurology, London WC1N 3BG, United Kingdom;

Department of Neurodegenerative Disease, University College London (UCL) Institute of Neurology, London WC1N 3BG, United Kingdom;

Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, United Kingdom;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
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Overexpression of the Hspa13 (Stch) gene reduces prion disease incubation time in mice

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