Atm deficiency results in severe meiotic disruption as early as leptonema of prophase I

Author:

Barlow C.1,Liyanage M.1,Moens P.B.1,Tarsounas M.1,Nagashima K.1,Brown K.1,Rottinghaus S.1,Jackson S.P.1,Tagle D.1,Ried T.1,Wynshaw-Boris A.1

Affiliation:

1. Genetic Disease Research Branch, Genome Technology Branch and Molecular Genetics and Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Infertility is a common feature of the human disorder ataxia-telangiectasia and Atm-deficient mice are completely infertile. To gain further insight into the role of ATM in meiosis, we examined meiotic cells in Atm-deficient mice during development. Spermatocyte degeneration begins between postnatal days 8 and 16.5, soon after entry into prophase I of meiosis, while oocytes degenerate late in embryogenesis prior to dictyate arrest. Using electron microscopy and immunolocalization of meiotic proteins in mutant adult spermatocytes, we found that male and female gametogenesis is severely disrupted in Atm-deficient mice as early as leptonema of prophase I, resulting in apoptotic degeneration. A small number of mutant cells progress into later stages of meiosis, but no cells proceed beyond prophase I. ATR, a protein related to ATM, DMC1, a RAD51 family member, and RAD51 are mislocalized to chromatin and have reduced localization to developing synaptonemal complexes in spermatocytes from Atm-deficient mice, suggesting dysregulation of the orderly progression of meiotic events. ATM protein is normally present at high levels primarily in ova cytoplasm of developing ovarian follicles, and in the nucleus of spermatogonia and to a lesser extent in spermatoctyes, but without localization to the synaptonemal complex. We propose a model in which ATM acts to monitor meiosis by participation in the regulation or surveillance of meiotic progression, similar to its role as a monitor of mitotic cell cycle progression.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

Reference31 articles.

1. The role of the Ataxia telangiectasia gene in the p53, WAF1/CIP1(p21)-and GADD45-mediated response to DNA damage produced by ionising radiation.;Artuso;Oncogene,1995

2. Genetic analysis of sex chromosomal meiotic mutants in Drosophila melanogaster.;Baker;Genetics,1972

3. Atm-deficient mice: a paradigm of ataxia telangiectasia.;Barlow;Cell,1996

4. Partial rescue of the severe prophase I defects of Atm -deficient mice by p53 and p21 null alleles.;Barlow;Nature Genet,1997

5. Atm selectively regulates distinct p53-dependent cell cycle checkpoint and apoptotic pathways.;Barlow;Nature Genet,1997

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