Oligo-astheno-teratozoospermia in mice lacking RA175/TSLC1/SynCAM/IGSF4A, a cell adhesion molecule in the immunoglobulin superfamily
Oligo-astheno-teratozoospermia in mice lacking RA175/TSLC1/SynCAM/IGSF4A, a cell adhesion molecule in the immunoglobulin superfamily
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DOI：
10.1128/mcb.26.2.718-726.2006
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发表时间：
2006-01-01
影响因子：
5.3
通讯作者：
Momoi, T
中科院分区：
文献类型：
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作者：
Fujita, E;Kouroku, Y;Momoi, T
RA175/TSLC1/SynCAM/IGSF4A （RA175）是免疫球蛋白超家族的一员，具有不依赖于Ca2+的亲同型跨细胞粘附活性，参与突触和上皮细胞连接。为了阐明RA175的生物学功能，我们破坏了小鼠Igsf4a （RA175 /Tslc1/SynCam/Igsf4a RA175）基因。缺乏两个Ra175等位基因（Ra175(-/-)）的雄性小鼠不育，表现为少弱畸形精子症；在附睾中几乎没有发现成熟的活动精子。杂合子雌雄和纯合子雌雄均可生育，无明显发育缺陷。RA175在野生型睾丸中主要表达于精母细胞、伸长和伸长精子的细胞交界处（步骤9 ~ 15）；RA175的表达仅限于远端（尾侧），而不局限于近端（头侧）。在Ra175（-/-）睾丸中，伸长的和成熟的精子（步骤13至16）几乎检测不到；圆形精子形态正常，但细长精子（步骤9至12）未能进一步成熟并转移到输卵管表面。在不合适的位置，剩余的细长精子最终被支持细胞吞噬。此外，未分化和异常的精子从外表面脱落进入管状管腔。因此，基于ra175的细胞连接对于保留长形精子在支持细胞内陷中的成熟和向外表面的移位以及时释放是必要的。
RA175/TSLC1/SynCAM/IGSF4A (RA175), a member of the immunoglobulin superfamilly with Ca2+-independent homophilic trans-cell adhesion activity, participates in synaptic and epithelial cell junctions. To clarify the biological function of RA175, we disrupted the mouse Igsf4a (Ra175/Tslc1/SynCam/Igsf4a Ra175) gene. Male mice lacking both alleles of Ra175 (Ra175(-/-)) were infertile and showed oligo-astheno-teratozoospermia; almost no mature motile spermatozoa were found in the epididymis. Heterozygous males and females and homozygous null females were fertile and had no overt developmental defects. RA175 was mainly expressed on the cell junction of spermatocytes, elongating and elongated spermatids (steps 9 to 15) in wild-type testes; the RA175 expression was restricted to the distal site (tail side) but not to the proximal site (head side) in elongated spermatids. In Ra175(-/-) testes, elongated and mature spermatids (steps 13 to 16) were almost undetectable; round spermatids were morphologically normal, but elongating spermatids (steps 9 to 12) failed to mature further and to translocate to the adluminal surface. The remaining elongating spermatids at improper positions were finally phagocytosed by Sertoli cells. Furthermore, undifferentiated and abnormal spermatids exfoliated into the tubular lumen from adluminall surfaces. Thus, RA175-based cell junction is necessary for retaining elongating spermatids in the invagination of Sertoli cells for their maturation and translocation to the adluminall surface for timely release.