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Molecular and Cellular Biology, February 2003, p. 1304-1315, Vol. 23, No. 4
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.4.1304-1315.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Mouse Germ Cell-Less as an Essential Component for Nuclear Integrity

Department of Molecular Cell Biology,¹ Department of Laboratory Sciences for Animal Experimentation, Research Institute for Microbial Diseases, Osaka University, Suita-shi, Osaka 565-0871,⁵ Department of Anatomy and Reproductive Cell Biology, Miyazaki Medical College, Kiyotake, Miyazaki 889-1692,² Department of Urology, Osaka University Medical School, Suita-shi, Osaka 565-0871,³ Genome Information Research Center, Osaka University, Suita-shi, Osaka 565-0871, Japan⁴

Received 19 September 2002/ Returned for modification 16 October 2002/ Accepted 18 November 2002

A mouse homologue of the Drosophila melanogaster germ cell-less (mgcl-1) gene is expressed ubiquitously, and its gene product is localized to the nuclear envelope based on its binding to LAP2ß (lamina-associated polypeptide 2ß). To elucidate the role of mgcl-1, we analyzed two mutant mouse lines that lacked mgcl-1 gene expression. Abnormal nuclear morphologies that were probably due to impaired nuclear envelope integrity were observed in the liver, exocrine pancreas, and testis. In particular, functional abnormalities were observed in testis in which the highest expression of mgcl-1 was detected. Fertility was significantly impaired in mgcl-1-null male mice, probably as a result of severe morphological abnormalities in the sperm. Electron microscopic observations showed insufficient chromatin condensation and abnormal acrosome structures in mgcl-1-null sperm. In addition, the expression patterns of transition proteins and protamines, both of which are essential for chromatin remodeling during spermatogenesis, were aberrant. Considering that the first abnormality during the process of spermatogenesis was abnormal nuclear envelope structure in spermatocytes, the mgcl-1 gene product appears to be essential for appropriate nuclear-lamina organization, which in turn is essential for normal sperm morphogenesis and chromatin remodeling.

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