Developmental expression, cellular localization, and testosterone regulation of alpha 1-antitrypsin in Mus caroli kidney.
alpha 1-Antitrypsin (alpha 1-protease inhibitor), an essential plasma protein, is synthesized predominantly in the liver of all mammals. We have previously shown that Mus caroli, a Southeast Asian mouse species is exceptional in that it expresses abundantly alpha 1-antitrypsin mRNA and polypeptide, in the kidney as well as the liver (Berger, F.G., and Baumann, H. (1985) J. Biol. Chem. 260, 1160-1165) providing a unique model for examination of the evolution of genetic determinants of tissue-specific gene expression. In the present paper, we have further characterized alpha 1-antitrypsin expression in M. caroli. The extrahepatic expression of alpha 1-antitrypsin is limited to the kidney, specifically within a subset of the proximal tubule cells. The developmental pattern of alpha 1-antitrypsin mRNA expression in the kidney differs from that in the liver. In the kidney, alpha 1-antitrypsin mRNA is present at only 2-4% adult level at birth and increases very rapidly to adult level during puberty between 26 and 36 days of age. There are no significant changes in liver alpha 1-antitrypsin mRNA levels during this period. Testosterone, while having only modest affects on alpha 1-antitrypsin mRNA accumulation in the adult kidney, causes a 20-fold induction of the mRNA in the pre-pubertal kidney. This suggests that the increase in alpha 1-antitrypsin mRNA expression during puberty is testosterone mediated. Southern blot analyses of Mus domesticus and M. caroli genomic DNA and a cloned M. caroli alpha 1-antitrypsin genomic sequence, indicate that a single alpha 1-antitrypsin gene exists in M. caroli, whereas multiple copies exist in M. domesticus. These data show that the alteration in tissue specificity of alpha 1-antitrypsin mRNA accumulation that has occurred during Mus evolution is associated with distinctive developmental and hormonally regulated expression patterns.
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000378:metabolism; D008810:Mice, Inbred C57BL / Q000378:metabolism; D008811:Mice, Inbred DBA / Q000378:metabolism; D009115:Muridae / Q000378:metabolism*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D012741:Sexual Maturation; D013739:Testosterone / Q000494:pharmacology*; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin; D013739:Testosterone