Transmission of amyloidosis in offspring of mice with AApoAII amyloidosis.

Pre-existing amyloid fibrils can induce further polymerization of endogenous precursor proteins in vivo. Thus, transmission of amyloid fibrils (AApoAII) may induce a conformational change in endogenous apolipoprotein A-II and accelerate amyloid deposition in mouse senile amyloidosis. To characterize transmissibility, we examined amyloidosis in the offspring of AApoAII-injected mother mice that possessed the amyloidogenic Apoa2(c) allele of the apolipoprotein A-II gene.

Induction of AApoAII amyloidosis by various heterogeneous amyloid fibrils.

Preformed amyloid fibrils accelerate conformational changes of amyloid precursor proteins and result in rapid extension of amyloid fibrils in vitro. We injected various kinds of amyloid fibrils into mice with amyloidogenic apoAII gene (Apoa2(C)). The most severe amyloid depositions were detected in the tissues of mice injected with mouse AApoAII(C) amyloid fibrils.

Amyloidosis modifier genes in the less amyloidogenic a/j mouse strain.

Apolipoprotein A-II is deposited as an amyloid fibril in aged mice (senile AApoAII amyloidosis). Although mouse strains with the apolipoprotein A-II c allele (Apoa2(c)) generally develop early-onset and severe senile amyloidosis, the A/J strain shows significantly less amyloid deposition. To identify genes that modify spontaneous amyloidosis development in the A/J mouse, we performed a genome-wide screening using hybrid mice derived from A/J and SAMP1 mice, which have Apoa2(c) and age-associated severe amyloid deposition.

Induction of protein conformational change in mouse senile amyloidosis.

Aggregated amyloid fibrils can induce further polymerization of precursor proteins in vitro, thus providing a possible basis for propagation or transmission in the pathogenesis of amyloidoses. Previously, we postulated that the transmission of amyloid fibrils induces conformational changes of endogenous amyloid protein in mouse senile amyloidosis (Xing, Y., Nakamura, A.