Single Nucleotide Variants (SNVs) Define Senescence-Accelerated SAMP8 Mice, a Model of a Geriatric Condition

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.