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Wild Type ApoA-II Gene Does Not Rescue Senescence-Accelerated Mouse (SAMP1) From Short Life Span and Accelerated Mortality

^a Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
^b Field of Regeneration Control, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan
^c Department of Aging Angiology, Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto, Japan
^d Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan

Keiichi Higuchi, Department of Aging Angiology, Research Center on Aging and Adaptation, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan E-mail: khiguchi{at}sch.md.shinshu-u.ac.jp.

Decision Editor: Jay Roberts, PhD

Biochemical and genetic data suggest that the Apoa2^c allele of the apolipoprotein A-II gene causes severe senile amyloidosis (AApoAII) in SAMP1, a mouse model for accelerated senescence. We analyzed the effects of replacement of Apoa2^c in SAMP1 mice with non-amyloidogenic Apoa2^b on amyloidosis, lipoprotein metabolism, and progression of senescence using a congenic strain, P1.R1-Apoa2^b, which has the Apoa2^b chromosome region of SAMR1 in the genome of SAMP1. Age-associated amyloid deposition was not observed, but plasma concentrations of apoA-II protein and HDL-cholesterol decreased with age in P1.R1-Apoa2^b. P1.R1-Apoa2^b showed lower scores of senescence than did SAMP1. However, the life span and mortality rate doubling time were similar in P1.R1-Apoa2^b and SAMP1. These results suggest that replacement of Apoa2^c with non-amyloidogenic Apoa2^b does not rescue SAMP1 mice from a short life span and accelerated mortality.