Transgenic mouse model of AA amyloidosis

AA amyloidosis can be induced in mice experimentally through injection of c ertain chemical or biological compounds. However, the usefulness of this ap proach is limited by its dependence on exogenous inflammatory agents that s timulate cytokines to increase the synthesis of precursor serum amyloid A ( SAA) protein and the transitory nature of the pathological fibrillar deposi ts. We now report that transgenic mice carrying the human interleukin 6 gen e under the control of the metallothionein-I promoter had markedly increase d concentrations of SAA and developed amyloid in the spleen, liver, and kid neys by 3 months of age. At the time of death about 6 months later, organs obtained from these animals had extensive amyloid deposits. This disease pr ocess was apparent radiographically using small-animal computer axial tomog raphy and magnetic resonance imaging equipment. The AA nature of the amyloi d was evidenced immunohistochemically and was unequivocally established by sequence analysis of protein extracted from the fibrils. The availability o f this unique in vivo experimental model of AA amyloidosis provides the mea ns to assess the therapeutic efficacy of agents designed to reduce or preve nt the fibrillar deposits found in AA and other types of amyloid-associated disease.