AA amyloidosis-resistant CE/J mice have Saa1 and Saa2 genes that encode an identical SAA isoform.

Abstract

The CE/J mouse strain is resistant to amyloid A protein (AA) amyloidosis. In contrast to AA amyloidosis-susceptible mouse strains that concomitantly express serum amyloid A precursor protein (SAA) types 1 and 2 isoforms encoded by the Saa1 and Saa2 genes, respectively, in response to inflammatory stimulation from the liver, CE/J mice express only a single SAA isoform named SAA2.2. In addition, CE/J mice uniquely possess a Q30L amino acid substitution in SAA2.2 that inhibits amyloidogenesis. To elucidate the genetic basis underlying the expression of only a single SAA isoform in this strain, we conducted PCR cloning and nucleotide sequencing of the Saa1 and Saa2 genes from the CE/J genome. We revealed that CE/J mice possess functional Saa1 and Saa2 genes. Intriguingly, the two genes were identical with respect to amino acid sequence, each encoding the SAA2.2 isoform. RT-PCR analysis of inflamed liver tissue from CE/J mice demonstrated that both genes are expressed at equivalent levels. Reporter assays revealed that promoter/enhancer sequences of Saa1 and Saa2 genes in CE/J are also functional. These results indicate that the SAA2.2 isoform in CE/J is a mixture of Saa1 and Saa2 gene products.