Wild type ApoA-II gene does not rescue senescence-accelerated mouse (SAMP1) from short life span and accelerated mortality.
Biochemical and genetic data suggest that the Apoa2c 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 Apoa2c in SAMP1 mice with non-amyloidogenic Apoa2b on amyloidosis, lipoprotein metabolism, and progression of senescence using a congenic strain, P1.R1-Apoa2b, which has the Apoa2b 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-Apoa2b. P1.R1-Apoa2b showed lower scores of senescence than did SAMP1. However, the life span and mortality rate doubling time were similar in P1.R1-Apoa2b and SAMP1. These results suggest that replacement of Apoa2c with non-amyloidogenic Apoa2b does not rescue SAMP1 mice from a short life span and accelerated mortality.
Wang
J
J
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
Matsushita
T
T
Kogishi
K
K
Xia
C
C
Ohta
A
A
Chiba
T
T
Nakamura
A
A
Kondo
H
H
Mori
M
M
Hosokawa
M
M
Higuchi
K
K
D000375:Aging / Q000235:genetics*; D000483:Alleles; D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics; D016633:Apolipoprotein A-II / Q000097:blood / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D003643:Death; D004195:Disease Models, Animal; D005260:Female; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D000685:Serum Amyloid A Protein / Q000235:genetics; D015996:Survival Rate; D013997:Time Factors
D000682:Amyloid; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D000685:Serum Amyloid A Protein