A molecular-pathologic approach to murine senile amyloidosis. Serum precursor-apolipoprotein A-II variant (Pro5----Gln) presents only in the senile amyloidosis-prone SAM-P/1 and SAM-P/2 mice.

Murine apolipoprotein (apo) A-II is a serum precursor of murine senile amyloid protein. We determined the primary structures of apo A-II in accelerated senescence-prone mice (SAM-P) characterized by a high frequency of age-associated systemic amyloidosis and accelerated senescence-resistance mice (SAM-R) in which senile amyloidosis occurred with a low incidence. Apo-A-II variant (Pro5----Gln) was found to be present only in the serum of SAM-P and not in that of SAM-R or other random bred slc:ICR mice. The apo A-II variant in the serum of SAM-P is identical to the murine senile amyloid fibril protein (ASSAM) derived from amyloid-deposited tissues of SAM-P. These findings proved that apo A-II deposits in tissues without degradation and this mutation (Pro5----Gln) probably have significant effects on the structure and function of apo A-II and would play a critical role in murine senile amyloidogenesis.