spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 3 December 2003
doi: 10.1242/dev.00888

Development 131, 131-142 (2004)
Published by The Company of Biologists 2004
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrowOA All Versions of this Article:
dev.00888v1
131/1/131    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sharan, S. K.
Right arrow Articles by Handel, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharan, S. K.
Right arrow Articles by Handel, M. A.

BRCA2 deficiency in mice leads to meiotic impairment and infertility

Shyam K. Sharan1,*, April Pyle2, Vincenzo Coppola1, Janice Babus3, Srividya Swaminathan1, Jamie Benedict3, Deborah Swing1, Betty K. Martin1, Lino Tessarollo1, Janice P. Evans4, Jodi A. Flaws3 and Mary Ann Handel2

1 Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute at Frederick, 1050 Boyles Street, Frederick, MD 21702, USA
2 Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA
3 Department of Epidemiology and Preventive Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA
4 Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA

* Author for correspondence (e-mail: ssharan{at}mail.ncifcrf.gov)

Accepted 29 September 2003

The role of Brca2 in gametogenesis has been obscure because of embryonic lethality of the knockout mice. We generated Brca2-null mice carrying a human BAC with the BRCA2 gene. This construct rescues embryonic lethality and the mice develop normally. However, there is poor expression of the transgene in the gonads and the mice are infertile, allowing examination of the function of BRCA2 in gametogenesis. BRCA2-deficient spermatocytes fail to progress beyond the early prophase I stage of meiosis. Observations on localization of recombination-related and spermatogenic-related proteins suggest that the spermatocytes undergo early steps of recombination (DNA double strand break formation), but fail to complete recombination or initiate spermiogenic development. In contrast to the early meiotic prophase arrest of spermatocytes, some mutant oocytes can progress through meiotic prophase I, albeit with a high frequency of nuclear abnormalities, and can be fertilized and produce embryos. Nonetheless, there is marked depletion of germ cells in adult females. These studies provide evidence for key roles of the BRCA2 protein in mammalian gametogenesis and meiotic success.

Key words: BRCA2, Spermatogenesis, Oogenesis, Meiosis, DNA repair






© The Company of Biologists Ltd 2004