|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 3 December 2003
doi: 10.1242/dev.00888
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
This article has been cited by other articles:
|
|
 |
|
  F. Yang, S. Eckardt, N. A. Leu, K. J. McLaughlin, and P. J. Wang Mouse TEX15 is essential for DNA double-strand break repair and chromosomal synapsis during male meiosis J. Cell Biol., February 25, 2008; 180(4): 673 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kuznetsov, M. Pellegrini, K. Shuda, O. Fernandez-Capetillo, Y. Liu, B. K. Martin, S. Burkett, E. Southon, D. Pati, L. Tessarollo, et al. RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in females J. Cell Biol., February 26, 2007; 176(5): 581 - 592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Deans, K. K. Khanna, C. J. McNees, C. Mercurio, J. Heierhorst, and G. A. McArthur Cyclin-Dependent Kinase 2 Functions in Normal DNA Repair and Is a Therapeutic Target in BRCA1-Deficient Cancers Cancer Res., August 15, 2006; 66(16): 8219 - 8226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A Smirnova, P. J Romanienko, P. P Khil, and R D. Camerini-Otero Gene expression profiles of Spo11-/- mouse testes with spermatocytes arrested in meiotic prophase I Reproduction, July 1, 2006; 132(1): 67 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Saeki, N. Siaud, N. Christ, W. W. Wiegant, P. P. W. van Buul, M. Han, M. Z. Zdzienicka, J. M. Stark, and M. Jasin Suppression of the DNA repair defects of BRCA2-deficient cells with heterologous protein fusions PNAS, June 6, 2006; 103(23): 8768 - 8773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. E. Cohen, S. E. Pollack, and J. W. Pollard Genetic Analysis of Chromosome Pairing, Recombination, and Cell Cycle Control during First Meiotic Prophase in Mammals Endocr. Rev., June 1, 2006; 27(4): 398 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A Morelli and P. E Cohen Not all germ cells are created equal: Aspects of sexual dimorphism in mammalian meiosis Reproduction, December 1, 2005; 130(6): 761 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-x. Tian, D. Rai, J. Li, C. Zou, Y. Bai, D. Wazer, V. Band, and Q. Gao BRCA2 Suppresses Cell Proliferation via Stabilizing MAGE-D1 Cancer Res., June 1, 2005; 65(11): 4747 - 4753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Aguilar-Mahecha, B. F. Hales, and B. Robaire Effects of Acute and Chronic Cyclophosphamide Treatment on Meiotic Progression and the Induction of DNA Double-Strand Breaks in Rat Spermatocytes Biol Reprod, June 1, 2005; 72(6): 1297 - 1304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Martin, N. Winkelmann, M. I. R. Petalcorin, M. J. McIlwraith, and S. J. Boulton RAD-51-Dependent and -Independent Roles of a Caenorhabditis elegans BRCA2-Related Protein during DNA Double-Strand Break Repair Mol. Cell. Biol., April 15, 2005; 25(8): 3127 - 3139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Barchi and M. Jasin Seeking new meiotic genes PNAS, December 23, 2003; 100(26): 15287 - 15289. [Full Text] [PDF]
|
|
