MRC National Institute for Medical Research, London

Science for Health

Main navigation

Research areas

Genetics and Development

Infections and Immunity

Neurosciences

Structural Biology

Paul Burgoyne group project:

A Y short arm gene required for the apoptotic response to sex chromosome univalence

In male mice with a single sex chromosome and a full complement of Y short arm genes (for example XSxr^αO males) there is apoptosis of spermatocytes at the first meiotic metaphase (MI); this is presumed to be a consequence of the triggering of an MI spindle checkpoint by the X-attached-Y univalent. Our analysis of Yp-gene deficient XSxr^bO,Eif2s3y transgenic males and XO,Sry,Eif2s3y double transgenic males (Mazeyrat et al, 2001) revealed a unique disruption of the MI spindle checkpoint/apoptotic elimination, such that most spermatocytes complete the first meiotic division, but then fail to progress through the second meiotic division. This disruption of normal MI checkpoint function must be due to a Y gene (other than Eif2s3y) that maps to the region of the mouse Y short arm that is deleted in Sxr^b. We have made transgenic lines for all the remaining genes from this region and are using these to identify the Y gene(s) responsible.

Reduced MI spermatocyte apoptosis in males lacking most Y short arm genes

Click image to view at full-size

In XSxr^αO males (left) nearly all MI spermatocytes are eliminated by apoptosis (green fluorescent cells). In XO,Sry,Eif2s3y double transgenic males (right), apoptosis is markedly reduced and most spermatocytes complete the first meiotic division.

Selected publications

Mazeyrat, S; Saut, N; Grigoriev, V; Mahadevaiah, SK; Ojarikre, OA; Rattigan, A; Bishop, C; Eicher, EM; Mitchell, MJ and Burgoyne, PS (2001)
A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis.
Nature Genetics 29, 49-53 PubMed abstract