Anti-APOA2 monoclonal antibody, clone 5G4

A congenic strain of mice with amyloidogenic apolipoprotein A-II (Apoa2c) on the genetic background of the amyloidosis-resistant SAM-R/1 strain was produced by 12 generations of backcrossing. Genome mapping using endogenous murine leukemia proviral markers was done in the congenic strain, termed R1.P1-Apoa2c. We confirmed that only a small region surrounding the apoA-II gene on chromosome 1 was transferred from the genome of the donor SAM-P/1 strain. The level and particle size of plasma high density lipoprotein were decreased in R1.P1-Apoa2c mice compared to those in the progenitor SAM-R/1 mice. The function of apoA-II can be studied using this strain of mice.

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.