Haldane's rule and heterogametic female and male sterility in the mouse

Failed genetic experiments or experiments designed for other purposes sometimes reveal novel genetic information. The interspecific cross between laboratory strain mice of the Mus musculus musculus/domesticus complex and the separate species M. spretus is known to produce fertile F1 females and sterile F1 males. Infertility of the interspecific F1 XY male is said to be an example of what has become known as Haldane's rule: "When in the F1 offspring of two different animal races one sex is absent, rare, or sterile, that sex is the heterozygous [heterogametic] sex." We attempted to use fertile single-X (or XO) female laboratory mice of the M. m. musculus/domesticus complex mated to M. spretus males to construct females with specific X chromosomes to study segregation distortion of X chromosome marker genes that we reported previously in crosses with the two species. We assumed that the interspecific F1 XO female would be fertile like the interspecific F1 XX female but, instead, we found that it is infertile. Haldane's rule is not specific to sex, but demonstration of this has required study of separate species pairs with heterogametic males or with heterogametic females. The fertile XO laboratory mouse is female, but it is also heterogametic, producing both X and nullo-X eggs. Infertility of both the interspecific and heterogametic F1 XO female and F1 XY male in the same cross between laboratory mice and M. spretus suggests that heterogamety is at the cause of the infertility. The most parsimonious interpretation is that there is an interaction between the single X and heterozygous or heterospecific autosomes that may affect the same fundamental step in both female and male meiosis in the interspecific F1 hybrid. This hypothesis is now testable in the mouse.Key words: interspecific crosses, mouse, Haldane's rule.