Analysis of the mechanism of misfolding to amyloid protein using mouse amyloidosis

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We studied mouse AApoAII amyloidosis to elucidate the common mechanism of valious amyloidosis. We obtained the following results,1)We found transmission of amyloidosis from old amyloid laden mice to young mice by eating feces of old mice.2)Injection of amyloid fibrils induced amyloidosis in normal and amyloidosis resistant mice.3)In situ hybridization analysis revealed that extra-hepatic synthesis of apoA-II may contribute amyloid fibril formation in the local tissues.4)We studied the induction of AApoAII amyloidosis by various kind of amyloid fibrils. All amyloid fibrils injected intravenously into mice induced amyloidosis. Injected amyloid fibrils settle to amyloidogenic tissues(the lungs, tongue, stomach ets.)and might act as template(seed)for amyloid fibril formation.5)Acceleration of amyloidosis was observed in R1.P1-Apoa2c mice born from the mother mice in which severe amyloidosis was induced by AApoAII injection.6)We found severe amyloidosis in C57BL mice with amyloid-resistant type A apoA-II reared in one animal center and no amyloid deposition in R1.P1-Apoa2c mice with amyloidogenic type C apoA-II reared in SPf condition.7)We tried to develop the therapeutic methods for amyloidosis. Injection of adeno-virus with amyloid resistant apoA-II cDNA, food containing safflower oil as a lipid inhibited amyloidosis in vivo and anti-oxidant(rifanpicine and NDGA)inhibited fibril formation in vivo.These results suggested that invasion of exogenous substances with amyloid-fibril-like structures may act as seeds and trigger the conformational change of endogenous amyloid protein to polymerize into amyloid fibril.Mouse amyloidosis is a good model for study of the relationship between genetic and environmental factors in pathology of diseases.