Single nucleotide variants (SNVs) define senescence-accelerated SAMP8 mice, a model of a geriatric condition

Delerue, Fabien, Sjollema, Geoff, Whittle, Belinda, Krueger, Sarah, Andrews, Dan and Goetz, Juergen (2013) Single nucleotide variants (SNVs) define senescence-accelerated SAMP8 mice, a model of a geriatric condition. Journal of Alzheimers Disease, 36 2: 349-363. doi:10.3233/JAD-130089


Author Delerue, Fabien
Sjollema, Geoff
Whittle, Belinda
Krueger, Sarah
Andrews, Dan
Goetz, Juergen
Title Single nucleotide variants (SNVs) define senescence-accelerated SAMP8 mice, a model of a geriatric condition
Journal name Journal of Alzheimers Disease   Check publisher's open access policy
ISSN 1387-2877
1875-8908
Publication date 2013-01
Year available 2013
Sub-type Article (original research)
DOI 10.3233/JAD-130089
Volume 36
Issue 2
Start page 349
End page 363
Total pages 15
Place of publication Amsterdam, Netherlands
Publisher I O S Press
Collection year 2014
Language eng
Abstract One of the major challenges in neurodegenerative research is modeling systemic aging. Here, senescence-accelerated mice such as the multigenic SAMP8 (senescence accelerated prone 8) mice are useful as they are characterized by an early manifestation of senescence that includes a shortened lifespan and impaired brain and immune functions. While SAMP8 mice are widely used tools to address aging and neurodegenerative conditions such as Alzheimer's disease (AD), the underlying gene mutations are not known. To make the SAMP8 strain a more versatile and useful research tool, we performed exome sequencing, using SAMR1 (senescence accelerated mouse resistant 1) mice as controls. We identified 51 SNVs (single nucleotide variants) that discriminate SAMP8 from SAMR1 mice. Using the prediction tool Polyphen2, we were able to subdivide the SNVs into four categories: splice variants, probably damaging, possibly damaging, and benign. Of these genes, a significant fraction is predicted to be expressed in the brain. Our data present these genes for a more detailed analysis in aging and neurodegeneration studies. They underscore the usefulness of SAMP8 mice as an animal model to study fundamental mechanisms of both aging and the pathogenesis of AD.
Keyword Alzheimer's disease
Exome sequencing
Mouse
Senescence
Sequence nucleotide variants
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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