International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Dr Rosemary Elliott
Roswell Park Cancer Inst.
Elm St. at Carlton St.
Buffalo, NY 14263

Co-Authors:  Tabaczynski D, Pazik J, and Hohman C
Institution:   Roswell Park Cancer Inst  

Entry into meiosis is lethal to spermatogonia in a synthetic mutant

Male F1 hybrids between inbred strains and M. macedonicus are sterile.  To determine the genetic basis for this sterility, (C57BL/6J x M. macedonicus)F1 females were mated to C57BL/10J.  A genome-wide scan with 92 SSLPs was performed for 141 male progeny of this cross and QTLs accounting for about 50% of the testis weight variance were identified on proximal Chrs 17 and X. 

To confirm these findings, a congenic line, C57BL/6.MAC-X has been constructed.  The congenic interval extends from position 0 to position 38 on Chr X.  Congenic males have testes weighing 0.05 gm, compared to weights of 0.2 gm for the parents,.  Adult testes contain Sertoli cells, meiotically dividing spermatozoa, many vacuoles, and rarely show meiotic metaphase I.  In juvenile testes the meiotic cells are enclosed in vacuoles and undergo cell death well before meiosis is complete.  At three weeks of age a dramatic destruction of meiotic cells can be observed. 

Males recombinant within the congenic interval show varying testis weights, and there appear to be a number of loci affecting testis weight and sperm production.  However, males congenic for an interval from map position 14 to 16 always have small testes.  Among the loci in this interval are the genes for the pro-apoptotic protein, PDCD8, alias MAIF, and the anti-apoptotic protein, BIRC4, alias MXIAP.   A subcongenic strain carrying just this 2 map unit interval from M..macedonicus is being bred.  Supported by NIH grant GM33160

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