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Regular Article |
a Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142
b Department of Obstetrics, Gynecology and Reproductive Sciences, and Departments of Physiology and Urology, University of California, San Francisco, California 94143-0720
c Department of Pathology and
d Department of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
e MRC Human Genetics Unit, Edinburgh, Scotland EH4 2XU, United Kingdom
ABSTRACT
The human DAZ gene family is expressed in germ cells and consists of a cluster of nearly identical DAZ (deleted in azoospermia) genes on the Y chromosome and an autosomal homolog, DAZL (DAZ-like). Only the autosomal gene is found in mice. Y-chromosome deletions that encompass the DAZ genes are a common cause of spermatogenic failure in men, and autosomal homologs of DAZ are essential for testicular germ cell development in mice and Drosophila. Previous studies have reported that mouse DAZL protein is strictly cytoplasmic and that human DAZ protein is restricted to postmeiotic cells. By contrast, we report here that human DAZ and human and mouse DAZL proteins are present in both the nuclei and cytoplasm of fetal gonocytes and in spermatogonial nuclei. The proteins relocate to the cytoplasm during male meiosis. Further observations using human tissues indicate that, unlike DAZ, human DAZL protein persists in spermatids and even spermatozoa. These results, combined with findings in diverse species, suggest that DAZ family proteins function in multiple cellular compartments at multiple points in male germ cell development. They may act during meiosis and much earlier, when spermatogonial stem cell populations are established.
First decision: 10 November 1999.
1 Supported by the National Institutes of Health.
2 Correspondence: Renee A. Reijo, Dept. of Ob/Gyn & RS, 513 Parnassus, Box 0720, HSW1480, University of California, San Francisco, CA 94143-0720. FAX: 415 476 6145; reijo{at}itsa.ucsf.edu
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