Syrian and Armenian hamsters differ in serum amyloid A gene expression. Identification of novel Syrian hamster serum amyloid A subtypes.

Amyloid A (AA) amyloidosis is widespread throughout the animal kingdom. Several factors including: 1) precursor production; 2) precursor structure; 3) precursor degradation; and 4) precursor/product interaction with the pentraxin serum amyloid P have been implicated in amyloidogenesis, but the exact sequence of events leading to AA fibril formation and deposition remains unclear. Most models of experimental amyloidosis, including golden Syrian hamsters (Mesocricetus auratus), involve massive and repeated inflammatory stimulation; however, the model of spontaneous amyloidosis with aging in female, but not male, Syrian hamsters permits analysis of amyloidogenic factors in the absence of inflammation. Another genus, the Armenian hamster (Cricetulus migratorius), differs from Syrian hamsters both in gender-specific serum amyloid P expression and susceptibility to AA amyloidosis. In this study, we describe novel SAA molecules in the Syrian hamster in the presence and absence of inflammation. We demonstrate that, based on isoelectric separation, the Syrian hamster SAA proteins can be separated into two broad subfamilies. Plasma SAA concentration in female Syrian hamsters increases spontaneously with age, and fragments of a basic SAA isotype expressed both hepatically and extrahepatically are selectively deposited as AA fibrils. After inflammatory stimulation, the patterns of SAA gene expression in Syrian and Armenian hamsters differ. In Syrian hamsters, both hepatic SAA mRNA and the high density lipoprotein apoSAA content increase approximately 1000-fold; in Armenian hamsters, hepatic SAA mRNA is limited in quantity and different in structure; and although plasma SAA proteins increase three- to fivefold, apoSAA is not detectable in high density lipoprotein. The results suggest that regulation and site of precursor production as well as precursor structure influence AA amyloidogenesis in these two hamster genera.