Weibel-Palade bodies and Golgi apparatus

Paul Burgoyne group project:

X-attached-Y/O males and the MI checkpoint response to univalent sex chromosomes

In 1982 we established that in male meiosis, X-Y PAR synapsis and/or crossing over was essential for fertility. In mice in which an X and/or Y chromosome is present that fails to achieve PAR synapsis and crossing over, as is the case in X-attached-Y/O males, there is spermatocyte loss due to apoptosis at MI. Although at the time we thought this MI apoptosis was a consequence of PAR asynapsis per se it is now clear that it is due to the presence of a sex chromosome univalent at the first meiotic metaphase, which triggers the MI spindle checkpoint and subsequent apoptotic elimination.  Although this checkpoint is undoubtedly a modification of the mitotic spindle checkpoint, there is much to be learnt about the molecular steps responsible for the MI arrest.

A number of years ago we established an exceptional pedigree of fertile X-attached-Y/O males that have a severely impaired MI checkpoint, and have determined that at least three genetic factors are involved. We are using a SNP-mapping approach to identify these factors and we have already mapped one of the factors to the tip of chromosome 5 where the known mitotic spindle checkpoint gene Mad1l1 is located. However, as yet we have been unable to find any alteration to Madl1 in mice from the exceptional pedigree.

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