International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

B30. Loci Affecting Male Sterility in Hybrids between Mus Macedonicus and C57BL/6

Rosemary W. Elliott, Diane Poslinski, Joanne Pazik and Verne M. Chapman
Roswell Park Cancer Inst., Buffalo NY 14263 USA

As with interspecies crosses involving Mus spretus, male F1 hybrids between inbred strains and Mus macedonicus are sterile. To determine the genetic basis for this sterility, (C57BL/6J x Mus macedonicus)F1 females were mated to males from C57BL/10J. Testis weight and body weight were determined and developing spermatozoa were examined on testes from 141 male progeny of this cross. In about half the male progeny no meiotic metaphase I was observed. About half of the animals that progressed through meiosis I showed other indications of low fertility and the balance appeared fertile. Animals with small testes produce few or no functional sperm and are usually sterile. A genome-wide scan with 92 SSLPs was performed and QTLs for testis weight, and body weight As in the F1 hybrids with M. spretus, the pseudoautosomal region on distal Chrs X and Y is also involved. On Chr 17 there is a QTL for testis weight. The QTLs on Chrs X and 17 together account for about 50% of the variance for testis weight.

To confirm and extend this finding, congenic lines for the proximal ends of Chrs 17 and X have been constructed. By the N8 generation, they were homozygous B/6 for at least 10 loci per autosome. The congenic interval for C57BL/6.MAC-X extends from position 0 to position 38. Males carrying this interval have testes weighing 0.05 gm, compared to weights of 0.2 gm for the parents and do not show meiotic metaphase I in testis spreads. The congenic interval for C57BL/6.MAC-17 extends from position 0 to position 23. Males homozygous for this interval have testis weights of 0.13 gm. They appear to mate normally, but are infertile and produce abnormal sperm. These phenotypes are male-specific, and congenic females are normally fertile.

For both congenic lines, subcongenic males are being analyzed to correlate phenotype with the genetic interval. This will allow us to identify candidate genes. Preliminary results indicate that the Chr X congenic region affects sperm number and structure as well as entry into meiosis. Supported by NIH grant GM33160.

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