Disruption of Genetic Interaction Between Two Autosomal Regions and the X Chromosome Causes Reproductive Isolation Between Mouse Strains Derived From Different Subspecies

• Published in: Genetics (Austin) Vol. 175; no. 1; pp. 185 - 197
• Main Authors: Oka, Ayako, Aoto, Toshihiro, Totsuka, Yoshikazu, Takahashi, Riichi, Ueda, Masatsugu, Mita, Akihiko, Sakurai-Yamatani, Noriko, Yamamoto, Hiromi, Kuriki, Satoshi, Takagi, Nobuo, Moriwaki, Kazuo, Shiroishi, Toshihiko
• Format: Journal Article
• Language: English
• Published: United States Genetics Soc America 01-01-2007; Genetics Society of America; Copyright © 2007 by the Genetics Society of America
• Subjects: Animals; Chromosomes; Crosses, Genetic; Eggs; Female; Fertility; Fertilization in Vitro; Genetic Linkage; Genetics; Genotype; Hybridization, Genetic; Inbreeding; Investigations; Male; Males; Mice - classification; Mice - genetics; Mice, Inbred C57BL; Mus musculus domesticus; Quantitative Trait Loci; Reproduction; Testis - physiology; X Chromosome; Y Chromosome - genetics
• ISSN: 0016-6731; 1943-2631; 1943-2631
• DOI: 10.1534/genetics.106.062976

Reproductive isolation that initiates speciation is likely caused by incompatibility among multiple loci in organisms belonging to genetically diverging populations. Laboratory C57BL/6J mice, which predominantly originated from Mus musculus domesticus, and a MSM/Ms strain derived from Japanese wild mice (M. m. molossinus, genetically close to M. m. musculus) are reproductively isolated. Their F1 hybrids are fertile, but successive intercrosses result in sterility. A consomic strain, C57BL/6J-ChrX(MSM), which carries the X chromosome of MSM/Ms in the C57BL/6J background, shows male sterility, suggesting a genetic incompatibility of the MSM/Ms X chromosome and other C57BL/6J chromosome(s). In this study, we conducted genomewide linkage analysis and subsequent QTL analysis using the sperm shape anomaly that is the major cause of the sterility of the C57BL/6J-ChrX(MSM) males. These analyses successfully detected significant QTL on chromosomes 1 and 11 that interact with the X chromosome. The introduction of MSM/Ms chromosomes 1 and 11 into the C57BL/6J-ChrX(MSM) background failed to restore the sperm-head shape, but did partially restore fertility. This result suggests that this genetic interaction may play a crucial role in the reproductive isolation between the two strains. A detailed analysis of the male sterility by intracytoplasmic sperm injection and zona-free in vitro fertilization demonstrated that the C57BL/6J-ChrX(MSM) spermatozoa have a defect in penetration through the zona pellucida of eggs.