Apolipoprotein A-II gene and development of amyloidosis and senescence in a congenic strain of mice carrying amyloidogenic ApoA-II.
BACKGROUND
Apolipoprotein A-II (ApoA-II), a major apoprotein of serum high density lipoprotein (HDL) deposits as an amyloid fibril (AApoAII) in murine senile amyloidosis. Type C ApoA-II gene (Apoa2c) in the SAMP1 strain of mice, a murine model of severe senile amyloidosis and accelerated senescence was transferred on the genetic background of the SAMR1 strain, in which senile amyloidosis is rare and has a normal aging process, and a congenic strain of mouse (R1.P1-Apoa2c) was developed (Higuchi K, Kitado H, Kitagawa K, Kogishi K, Naiki H, Takeda T. FEBS Lett 1993;317:207-10).


METHODS
We identified AApoAII amyloid deposits in the 14-month-old congenic R1.P1-Apoa2c strain and compared these findings with the deposits in the progenitor SAMP1 and SAMR1 strains. The progression of senescence was estimated using a grading system and the age-associated changes in the metabolism of ApoA-II and HDL were investigated in the three strains of mice.


RESULTS
At 14 months of age, severe amyloid deposition as compared with the donor SAMP1 strain was present in the congenic R1.P1-Apoa2c strain, but AApoAII was not evident in the progenitor SAMR1 strain which has type B ApoA-II. No obvious differences in the progression of senescence were observed between the R1.P1-Apoa2c and SAMR1 strains. In the R1.P1-Apoa2c strain, the serum HDL-cholesterol concentrations decreased in parallel with ApoA-II levels with advancing age and the decrease was much accelerated compared with the decrease seen in SAMR1 mice.


CONCLUSIONS
Based on these results, we propose that the genetic type of ApoA-II plays an important role in the development of senile amyloidosis and age-associated changes in HDL metabolism. However, it has a minor role in the accelerated senescence in the mouse strains we used.
Higuchi
K
K
Department of Senescence Biology, Kyoto University, Japan.
Naiki
H
H
Kitagawa
K
K
Kitado
H
H
Kogishi
K
K
Matsushita
T
T
Takeda
T
T
D000375:Aging / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism*; D000818:Animals; D016633:Apolipoprotein A-II / Q000235:genetics* / Q000378:metabolism*; D001345:Autoradiography; D002874:Chromosome Mapping; D008074:Lipoproteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains
D016633:Apolipoprotein A-II; D008074:Lipoproteins