MEIOTIC ABNORMALITIES IN HYBRID MICE OF THE C57BL 6J X MUS-SPRETUS CROSS SUGGEST A CYTOGENETIC BASIS FOR HALDANE RULE OF HYBRID STERILITY/

Light- and electron-microscopic analyses of chromosomal pairing and re combination in F1 and first-backcross generation mice of the C57BL/6J x Mus spretus cross revealed a variety of meiotic irregularities that could contribute to meiocyte loss and infertility. Pachytene anomalies included univalency, partially paired bivalents, homolog-length inequ alities, nonhomologous pairing, and associations of asynapsed autosoma l segments with the X chromosome. These phenomena were most prevalent in F1 males, which are invariably sterile. Although F1 females were qu alitatively fertile, breeding data indicated significant reproductive impairment. Molecular analyses of X-linked and pseudoautosomal loci in sterile and fertile backcross males revealed that the failure of X-Y pairing and recombination is correlated with heterozygosity within the pseudoautosomal regions of the X and Y chromosomes. In addition to im pairing fertility, the synaptic disturbances (such as localized asynap sis and nonhomologous pairing) observed in F1 individuals can potentia lly alter recombinational patterns, thereby contributing to the geneti c-map distortion observed with this interspecific cross. Together, the cytogenetic and reproductive data suggest that sex-related difference s in the gametogenic process, quantitative differences in the incidenc e of synaptic irregularities in female and male meiosis, and phenomena associated with the X and Y chromosomes comprise the etiological basi s of the sex-biased F1 sterility. The differential gender-related effe cts of these cytogenetic phenomena may constitute the underlying basis of Haldane's rule in mammals.