Extrahepatic Expression of Apolipoprotein A-II in Mouse Tissues: Possible Contribution to Mouse Senile AmyloidosisLi Fua, Ikuo Matsuyamac, Takuya Chibaa, Yanming Xinga, Tatsumi Korenagaa, Zhanjun Guoa, Xiaoying Fua, Jun Nakayamab, Masayuki Moria, and Keiichi Higuchiaa Department of Aging Angiology, Shinshu University School of Medicine, Matsumoto b Research Center on Aging and Adaptation and Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto c Division of Clinical Pathology, Nagano Cancer Detection Center, Matsumoto, Japan Correspondence to: Keiichi Higuchi, Dept. of Aging Angiology, Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto 390-8621, Japan. E-mail: khiguchi@sch.md.shinshu-u.ac.jp Apolipoprotein A-II (apoA-II), an apolipoprotein in serum high-density lipoprotein, is a precursor of mouse senile amyloid fibrils. The liver has been considered to be the primary site of synthesis. However, we performed nonradioactive in situ hybridization analysis in tissue sections from young and old amyloidogenic (R1.P1-Apoa2C) 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 epithelium and the chief cells of the fundic gland in the stomach, the crypt cells and a small portion of the absorptive epithelial cells in the small intestine, the basal cells of the tongue mucosa, and the basal cells of the epidermis and hair follicles in the skin in both mouse strains. Expression of apoA-II mRNA in those tissues was also examined by RT-PCR analysis. Immunolocalization of apoA-II protein also indicated the cellular localization of apoA-II. ApoA-II transcription was not observed in the heart. Amyloid deposition was observed around the cells expressing apoA-II mRNA in the old R1.P1-Apoa2C mice. These results demonstrate that the apoA-II mRNA is transcribed and translated in various extrahepatic tissues and suggest a possible contribution of apoA-II synthesized in these tissues to amyloid deposition. (J Histochem Cytochem 49:739747, 2001) Key Words: amyloidosis, mouse, apoA-II mRNA, in situ hybridization
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