International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

A20. Males of X-Chromosome Consomic Strain, B6.MSM-Chr.X, Show Spermatozoa Malformation and Sterility: Phenotype Characterization and Mapping of Responsible Gene(s)

Ayako Oka1, Akihiko Mita1, Yoichi Mizushina1, Kiyotaka Toshimori2 and Toshihiko Shiroishi1.
1Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, Japan;
Department of Anatomy and Cell Biology, Miyazaki Medical College, Miyazaki-ken, Japan.

We have set out construction of a full set of consomic strains, substituting each chromosome of Japanese wild mouse (Mus musuculus molossinus)-derived MSM strain for the corresponding chromosome of C57BL/6J (B6) strain. Since the most of genes in B6 strain are originated from European subspecies, Mus musculus domesticus, the genes in two mouse strains are estimated to be diverged for a long evolutionary period, approximately one million years. During the process of generating of X-chromosome consomic strain, B6.MSM-Chr.X, we noticed that males of the strain have lowered fertility. It seemed due to the disturbance of coordination between gene(s) in the X-chromosome of MSM strain and the autosomal gene(s) of B6 strain. Males of B6.MSM-Chr.X show severe reproductive defect. In vitro fertilization using sperms prepared from the consomic males indicated a low fecundity as well. This defect became more emphasized as progression of the backcross generations. Spermatozoa of the consomic males show morphological anomaly and low motility at high frequency. Moreover, their testes have reduced weight and different degree of abnormalities. To identify X-chromosomal gene(s) responsible for these anomalies in spermatozoa and the testes, quantitative trait loci (QTL) analysis was carried out based on the progeny of the backcross generations N3 and N4. This study indicated two significant QTLs, strong one at a central region and modest one at a distal region on X-chromosome. When similar QTL analysis was applied to the testis weight, another QTL was detected at a distal region on X-chromosome, which is distinct from the QTL that controls spermatozoa morphology. Understanding the mechanism by which the coordination between X-chromosome and autosomes is disrupted in the B6.MSM-Chr.X might give us an insight into the genetic regulation in the terminal differentiation of male germline cells, and the genetic differentiation or speciation of mice in the evolutionary process.

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