HIGH-RESOLUTION MAPPING OF SPERM FUNCTION DEFECTS IN THE T-COMPLEX 4TH-INVERSION

Structural variants of the mouse Chr 17-specific t complex, known as t haplotypes, express factors that alter the ability of sperm to carry out their roles in the normal fertilization process. In previous studi es of males carrying heterospecific combinations of the t complex, we discovered a unique M. spretus/t haplotype phenotype of male sterility . In additional studies with mice carrying a series of M. spretus-M. m . domesticus recombinant Chr 17 homologs and a complete t haplotype (S -+/t), we monitored physiological aspects of sperm function to map a l ocus (Hst6) responsible for expression of the t-specific ''curlicue'' sperm flagellar curvature phenotype to 1 cM within the fourth inversio n of the t complex. In the present report, we quantitatively analyze t he in vitro capability of sperm from mice with similar S-+/t Chr 17 ge notypes to fertilize zona pellucida-free mouse eggs. The results ident ify a locus, Stop1, mapping distal to Pim1, with acute effects on the ability of sperm to penetrate the oolemma. The data suggest that Stop1 is a complex locus consisting of at least two genetic elements, a pro ximal one overlapping the Hst6 locus, and another, distal to the Hst6 locus. Further quantitative analyses of the ''curlicue'' phenotype pro duced by sperm derived from these same animals indicate that expressio n of this chronic flagellar curvature phenotype also derives from at l east two elements, both mapping within the Hst6 locus. Thus, these stu dies provide higher resolution mapping of the molecular basis of t hap lotype-specific sperm dysfunction emanating from In(17)4.