Diversity and Complexity of the Mouse Saa1 and Saa2 genes

Mouse strains show polymorphisms in the amino acid sequences of serum amyloid A 1 (SAA1) and serum amyloid A 2 (SAA2). Major laboratory mouse strains are classified based on the sequence as carrying the A haplotype (e.g., BALB/c) or B haplotype (e.g., SJL/J) of the Saa1 and Saa2 gene unit. We attempted to elucidate the diversity of the mouse Saa1 and Saa2 family genes at the nucleotide sequence level by a systematic survey of 6 inbred mouse strains from 4 Mus subspecies, including Mus musculus domesticus, Mus musculus musculus, Mus musculus castaneus, and Mus spretus. Saa1 and Saa2 genes were obtained from the mouse genome by PCR amplification, and each full-length nucleotide sequence was determined. We found that Mus musculus castaneus mice uniquely possess 2 divergent Saa1 genes linked on chromosome 7. Overall, the mouse strains had distinct composite patterns of amino acid substitutions at 9 positions in SAA1 and SAA2 isoforms. The mouse strains also had distinct composite patterns of 2 polymorphic upstream regulatory elements that influenced gene transcription in in vitro reporter assays. B haplotype mice were revealed to possess an LTR insertion in the downstream region of Saa1. Collectively, these results indicate that the mouse Saa genes hold broader diversity and greater complexity than previously known, and these characteristics were likely attained through gene duplication and repeated gene conversion events in the Mus lineage.