Structure of the MouseSaa4Gene and Its Linkage to the Serum Amyloid A Gene Family

Abstract

The serum amyloid A (SAA) proteins are a polymorphic family of apolipoproteins associated with high-density lipoproteins (HDL). Three distinct subfamilies have been identified: (i) a cytokine-induced acute phase subfamily that is hepatically produced and can become the major apolipoprotein on HDL (SAA1, SAA2); (ii) a peripherally produced acute phase SAA3 that is only a minor HDL apolipoprotein; and (iii) a constitutive subfamily (SAA4) that is a minor normal HDL apolipoprotein comprising more than 90% of the SAA during homeostasis. Here we define the structure of theSaa4gene. Similar to other Saa family members, it has four exons and three introns. It is 4588 bp long from the transcription start site to the end of the 3′-untranslated region and is approximately 20% larger than otherSaagenes. We have locatedSaa411 kb upstream fromSaa3and 5 kb downstream fromSaa1,with the pseudogene approximately 1 kb from the 5′ end ofSaa4. Saa4has the same orientation as most otherSaafamily members, with onlySaa2having an opposing orientation. These data promote our understanding of the evolution of theSaafamily. They enhance our ability to develop the mouse as a transgenic and gene deletion model to advance the understanding of the function of these apolipoproteins.