| Summary: | 博士 === 臺北醫學大學 === 醫學研究所 === 92 === Growth-arrest-specific (Gas) genes are expressed during serum starvation or contact inhibition of cells grown in culture. Here we report the isolation and characterization of Gas8, a novel gene identified on the basis of its growth-arrest-specific expression in murine fibroblasts. Gas8 is located at the terminus of mouse chromosome 8. Recently, Gas8 homologues were found in Homo sapiens, Rattus norvegicus, Drosophila melanogaster, Anopheles gambiae, Danio rerio, Chlamydomonas reinhardi, and Trypanosoma brucei. We show that production of Gas8 mRNA and protein occurs in adult mice predominantly in the testes, where expression is regulated during post-meiotic development of male gametocytes. Whereas a low level of Gas8 mRNA was detected by Northern blotting in testes of murine male neonates and young adolescents, Gas8 mRNA increased rapidly post-meiotically. In adult males, both Gas8 mRNA and protein reached steady state levels in testes that were 10 fold higher than in other tissues. Immunohistochemical analyses showed that Gas8 protein accumulates in gametocytes as they approach the lumen of seminiferous tubules and was localized to the cytoplasm of round spermatids, the tails of elongating spermatids, and mature spermatid tail bundles protruding into the lumen; in epididymal spermatozoa Gas8 protein was present in the flagella. However, pre-meiotic murine gametocytes lacked detectable Gas8 protein, as did seminiferous tubules in biopsy specimens from seven human males having cytological evidence of non-obstructive azoospermia secondary to Sertoli cell only syndrome. Our findings, which associate Gas8 production developmentally with the later stages of spermatogenesis and spatially with the sperm motility apparatus, collectively suggest that this growth-arrest-specific gene product may have a role in sperm motility and male fertility. This postulated role for Gas8 is supported by our observation that highly localized production of Gas8 protein occurs also in the cilia of epithelial cells lining pulmonary bronchi and fallopian tubes, and by the flagellar association and motility function of a Chlamydomonas reinhardi ortholog (PF2) of Gas8. Because new studies on several fronts have revealed that mutations in cilia/basal body proteins are responsible for cilia-related human disorders such as polycystic kidney disease, primary ciliary dyskinesia, Kartagener syndrome, and Bardet-Biedl syndrome, the role of Gas8 in these human disorder deserves further investigation.
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