精子细胞
生物
顶体
细胞生物学
精子发生
精子
基因剔除小鼠
鬼臼苷
精子发生
肌动蛋白
细胞质
男科
细胞骨架
遗传学
基因
内分泌学
细胞
医学
作者
Tracy M. Clement,Chris Geyer,William H. Willis,Eugenia H. Goulding,Mitch Eddy
标识
DOI:10.1093/biolreprod/87.s1.140
摘要
During spermiogenesis round spermatids differentiate into elongated and then condensed spermatids followed by spermiation. Although the structural components and morphological changes in this complex process have been described in detail, relatively little is known about the mechanisms that drive these structural changes. The involvement of filamentous actin (F-actin) has been suggested for several aspects of spermatid differentiation, including acrosome formation and attachment to the nucleus, formation of tubulobulbar complexes and cytoplasmic removal, and spermiation. In addition, human male infertility is often associated with a high incidence of abnormally shaped sperm heads, suggesting that cytoskeletal regulation is important for male fertility. Actin-like 7b (Actl7b) is an intronless gene expressed in spermatids and conserved in mammals. Immunohistochemistry and indirect immunofluorescence were utilized to investigate the expression of ACTL7B. It is localized in the cytoplasm of round and elongating spermatids and co-localizes with phalloidin labeled F-actin) in or around the forming acrosome, suggesting a role in this process. To determine the functional relevance of (Actl7b), knockout mice were generated from targeted ES cells in which the (Actl7b) coding region was replaced with a LacZ reporter sequence, obtained from the KnockOut Mouse Project (KOMP) Repository. X-gal staining of tissues from heterozygous animals revealed that (Actl7b) is expressed in the testis and, unexpectedly, the brain. While (Actl7b) knockout mice develop to adulthood and appear normal, breeding studies revealed that (Actl7b) knockout males mate and produce vaginal plugs, but are infertile. Testis and epididymal weights and sperm counts are lower in knockout males than in wild type males. In addition, sperm heads are misshapen with a rounded appearance. Most of these sperm are immotile, with less than three percent showing minimal flagellar movement. These results indicate that ACTL7B is required for spermatid morphogenesis, sperm motility, and male fertility. They also suggest that ACTL7B is either the F-actin recognized by phalloidin or is required for F-actin assembly in spermatids. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (EME).
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