RT Journal Article SR Electronic T1 Disruption of Genetic Interaction Between Two Autosomal Regions and the X Chromosome Causes Reproductive Isolation Between Mouse Strains Derived From Different Subspecies JF Genetics JO Genetics FD Genetics Society of America SP 185 OP 197 DO 10.1534/genetics.106.062976 VO 175 IS 1 A1 Oka, Ayako A1 Aoto, Toshihiro A1 Totsuka, Yoshikazu A1 Takahashi, Riichi A1 Ueda, Masatsugu A1 Mita, Akihiko A1 Sakurai-Yamatani, Noriko A1 Yamamoto, Hiromi A1 Kuriki, Satoshi A1 Takagi, Nobuo A1 Moriwaki, Kazuo A1 Shiroishi, Toshihiko YR 2007 UL http://www.genetics.org/content/175/1/185.abstract AB 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-ChrXMSM, 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-ChrXMSM 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-ChrXMSM 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-ChrXMSM spermatozoa have a defect in penetration through the zona pellucida of eggs.