title: The molecular basis of "curlicue": a sperm motility abnormality linked to the sterility of t haplotype homozygous male mice.
abstract: The t complex, a variant region of chromatin occupying approximately 40-million base pairs of proximal chromosome 17, exists in natural populations of wild mice of the Mus musculus species as a family of homologues called t haplotypes (t). Relative to wild-type (+) homologues, all t haplotypes share four large non-overlapping inversions, spanning 95% of the region, leading to intra-inversion recombination suppression in +/t heterozygotes. Non-lethal t homozygous males or complementing recessive lethal t doubly heterozygous males (hereafter both abbreviated "t/t males") are invariably and completely sterile, due to expression of several sperm function abnormalities. One of these traits, "curlicue", describes a condition in which spermatozoa from t/t males fail to reach the site of fertilization in vivo because they exhibit a severe loss of vigorous forward motility due to the chronic negative curvature of their flagella. Current data indicate that "curlicue" is the complex phenotypic reflection of the expression of three or more mutations clustered in the distal one-third of the largest and most-distal t complex inversion, In(17)4. From proximal to distal, candidates include Dnahc8, Tsga2 and Tctex5. Interestingly, new results from high-resolution intra-inversion genetic mapping and protein localization studies suggest that the products of the distal two candidates, Tsga2 and Tctex5, might play synergic roles in the expression of both the "curlicue" motility abnormality and the "stop" sperm-egg interaction aberration, regarded as functionally unrelated traits.
authors.affiliation: Dept of Anatomy and Cell Biology, School of Medicine, Temple University, 3400 N Broad St, Philadelphia, PA 19140, USA. stephen.pilder@temple.edu
authors.forename: S H
authors.initials: SH
authors.lastname: Pilder
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.forename: L
authors.initials: L
authors.lastname: Hui
authors.forename: S A
authors.initials: SA
authors.lastname: Samant
authors.forename: O O
authors.initials: OO
authors.lastname: Olugbemiga
authors.forename: K W
authors.initials: KW
authors.lastname: Meyers
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: S
authors.initials: S
authors.lastname: Vijayaraghavan
mesh_terms: D000818:Animals; D006239:Haplotypes; D006720:Homozygote; D007248:Infertility, Male / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D054645:Protein Phosphatase 1; D017422:Sequence Analysis, DNA; D013081:Sperm Motility / Q000276:immunology*; D013082:Sperm Tail / Q000473:pathology; D044767:Ubiquitin-Protein Ligases; D056427:t-Complex Genome Region
chemical_list: D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C533391:Ppp1r11 protein, mouse; D044767:Ubiquitin-Protein Ligases; D054645:Protein Phosphatase 1