The mouse t complex distorter/sterility candidate, Dnahc8, expresses a γ-type axonemal dynein heavy chain isoform confined to the principal piece of the sperm tail

AbstractHeterozygosity for a t haplotype (t) in male mice results in distorted transmission (TRD) of the t-bearing chromosome 17 homolog to their offspring. However, homozygosity for t causes male sterility, thus limiting the spread of t through the population at large. The Ca2+-dependent sperm tail curvature phenotypes, “fishhook”, where abnormally high levels of sperm exhibit sharp bends in the midpiece, and “curlicue”, where motile sperm exhibit a chronic negative curving of the entire tail, have been tightly linked to t-associated male TRD and sterility traits, respectively. Genetic studies have indicated that homozygosity for the t allele of Dnahc8, an axonemal γ-type dynein heavy chain (γDHC) gene, is partially responsible for expression of “curlicue”; however, its involvement in “fishhook”/TRD, if any, is unknown. Here we report that the major isoform of DNAHC8 is copiously expressed, carries an extended N-terminus and full-length C-terminus, and is stable and equally abundant in both testis and sperm from +/+ and t/t animals. By in silico analysis we also demonstrate that at least three of the seventeen DNAHC8t mutations at highly conserved positions in wild-type DHCs may be capable of substantially altering normal DNAHC8 function. Interestingly, DNAHC8 is confined to the principal piece of the sperm tail. The combined results of this study suggest possible mechanisms of DNAHC8t dysfunction and involvement in “curlicue”, and support the hypothesis that “curlicue” is a multigenic phenomenon. They also demonstrate that the accelerated “fishhook” phenotype of sperm from +/t males is not directly linked to DNAHC8t dysfunction