MOUSE SENILE AMYLOIDOSIS - ASSAM AMYLOIDOSIS IN MICE PRESENTS UNIVERSALLY AS A SYSTEMIC AGE-ASSOCIATED AMYLOIDOSIS

Amyloid deposition in 11 inbred strains of mice (A/J, SJL/J, DDD, C57BL/6J, B10.BR, C57BL/10, B10A/SgSn, C3H/HeMs, B10A(5R), DBA/2 and C57BL/6Cr5/c) was studied using the peroxidase antiperoxidase (PAP) method and antisera against AS(SAM) and murine protein AA. Among the 170 mice examined, in 77 (45.3%) from the nine strains other than C3H/HeMs and DBA/2, there was evidence of spontaneous amyloid deposits in routine histological sections. Immunohistochemical studies using 54 mice with amyloid deposition, demonstrated AS(SAM) deposition in 45 mice (83.3%) in all nine strains, although the incidence and intensity of the deposition differed somewhat between strains. SJL/J and A/J had AS(SAM) deposits from the age of 8 months and the incidence increased with advancing age. In the other seven strains, AS(SAM) was first deposited at an older age than in the SJL/J and A/J strains. In A/J, C57BL/6J, C57BL/10, B10.BR, B10A(5R) and C57BL/6Cr5/c, protein AA often coexisted with AS(SAM). The distribution pattern of the AS(SAM) deposits was similar to that observed among the SAM strains. Thus, AS(SAM) is an ubiquitously distributed senile amyloid protein in the mouse. Determination of the molecular type of apoA-II, a serum precursor of AS(SAM), among all 11 strains using the polymerase chain reaction (PCR) revealed the SAM-P/1 type apoA-II variant in SJL/J and A/J strains with a high susceptibility to AS(SAM) deposition. We concluded from this study that amino acid substitution in precursor apoA-II may be responsible for the early onset and severe amyloid deposition in the mouse.