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Amyloid A (AA) amyloidosis, a fatal systemic amyloid disease, occurs secondary to chronic inflammatory conditions in humans. Although persistently elevated serum amyloid A (SAA) levels are required for its pathogenesis, not all individuals with chronic inflammation necessarily develop AA amyloidosis. Furthermore, many diseases in cats are associated with the elevated production of SAA, whereas only a small number actually develop AA amyloidosis. We hypothesized that a genetic mutation in the SAA gene may strongly contribute to the pathogenesis of feline AA amyloidosis. In the present study, genomic DNA from four Japanese domestic cats (JDCs) with AA amyloidosis and from five without amyloidosis was analyzed using polymerase chain reaction (PCR) amplification and direct sequencing. We identified the novel variation combination of 45R-51A in the deduced amino acid sequences of four JDCs with amyloidosis and five without. However, there was no relationship between amino acid variations and the distribution of AA amyloid deposits, indicating that differences in SAA sequences do not contribute to the pathogenesis of AA amyloidosis. Immunohistochemical analysis using antisera against the three different parts of the feline SAA protein-i.e., the N-terminal, central, and C-terminal regions-revealed that feline AA contained the C-terminus, unlike human AA. These results indicate that the cleavage and degradation of the C-terminus are not essential for amyloid fibril formation in JDCs.

Chickens (Gallus gallus domesticus) can suffer from AA amyloidosis featuring the joints as major targets of amyloid accumulation. Analysis of post-mortem recordings from commercial chickens revealed that amyloid arthropathy frequently occurred in brown layer chickens, but never in white layers. The suspected higher susceptibility of brown layers was confirmed experimentally by inducing amyloidosis with an arthropathic and amyloidogenic strain of E. faecalis. Sequence analysis of cDNA coding for SAA, the amyloid precursor protein, revealed that the SAA proteins are identical in both breeds, although some nucleotide differences existed in the untranslated regions of the mRNAs. The chicken SAA gene was found to be a single copy gene which comprises 4 exons. The first of these exons apparently occupies a conserved position and is not translated. Investigation of the affected joints using in situ hybridization demonstrated local SAA gene expression. It is concluded that the likelihood of an E. faecalis induced arthritis to progress to amyloidosis is breed-dependent, but is not a consequence of a more amyloidogenic SAA.