Extrahepatic expression of apolipoprotein A-II in mouse tissues: Possible contribution to mouse senile amyloidosis

Apolipoprotein A-II (apoA-II), an apolipoprotein in serum high-density lipo protein, is a precursor of mouse senile amyloid fibrils. The liver has been considered to be the primary site of synthesis. However, we performed nonr adioactive in situ hybridization analysis in tissue sections from young and old amyloidogenic (R1.P1-Apoa2(C)) and amyloid-resistant (SAMR1) mice and revealed that other tissues in addition to the liver synthesize apoA-II. We found a strong hybridization signal in the basal cells of the squamous epi thelium and the chief cells of the fundic gland in the stomach, the crypt c ells and a small portion of the absorptive epithelial cells in the small in testine, the basal cells of the tongue mucosa, and the basal cells of the e pidermis and hair follicles in the skin in both mouse strains. Expression o f apoA-II mRNA in those tissues was also examined by RT-PCR analysis. Immun olocalization of apoA-II protein also indicated the cellular localization o f apoA-II. ApoA-II transcription was not observed in the heart. Amyloid dep osition was observed around the cells expressing apoA-II mRNA in the old R1 .P1-Apoa2(C) mice. These results demonstrate that the apoA-II mRNA is trans cribed and translated in various extrahepatic tissues and suggest a possibl e contribution of apoA-II synthesized in these tissues to amyloid depositio n.