Genes in the first and fourth inversions of the mouse t complex synergistically mediate sperm capacitation and interactions with the oocyte.
The t haplotypes (t) are recent evolutionary derivatives of an alternate form of the mouse t complex region located at the proximal end of chromosome 17. This variant form of approximately 1% of the mouse genome is a source of mutations altering numerous sperm functions crucial for fertilization. Males that carry two t haplotypes (t/t) are invariably sterile. t haplotypes contain four inversions relative to the wild-type t complex (+), so that in matings involving a +/t heterozygote, t is usually transmitted as a single unit. However, rare recombinants have been recovered, which carry only part of the t genotype and express only some of the t-dependent phenotypes. Use of these partial t haplotypes in genetic crosses has resulted in the general location of the two major t male sterility factors, S1 and S2, within inversions 1 and 4, respectively. Since sterility can result from a plethora of sperm defects, we have made a detailed study of various functional parameters of sperm from mice carrying S1 or S2 heterozygously or homozygously or in combination. Both S1 and S2 contain mutations altering sperm functions, including motility, capacitation, binding to the zona pellucida, binding to the oocyte membrane, and penetration of the zona pellucida-free oocyte. Therefore it seems clear that each of these factors contains multiple genes contributing to sterility. Furthermore, our results indicate that genes within S1 interact with genes in S2 for all sperm functions examined. However, S1 and S2 genes affecting motility interact in a purely additive fashion, while S1 and S2 genes affecting most other sperm characteristics interact in a synergistic manner. Additionally, the patterns of synergism between S1 and S2 for abnormalities in capacitation, sperm-oolemma binding, and zona-free oocyte penetration are nearly identical. This suggests that these three defects are caused by mutation of the same gene within each sterility factor. These findings will not only be instrumental in matching the various t haplotype sperm defects to candidate genes for S1 and S2, but will facilitate a more comprehensive understanding of the cellular and genetic mechanisms underlying t haplotype male sterility.
Redkar
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Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
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Twine
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Pilder
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Olds-Clarke
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D000177:Acrosome / Q000502:physiology; D000818:Animals; D021461:Animals, Outbred Strains; D002462:Cell Membrane / Q000378:metabolism; D007446:Chromosome Inversion; D003433:Crosses, Genetic; D003434:Crossing Over, Genetic; D004843:Epistasis, Genetic; D005260:Female; D005307:Fertilization in Vitro; D014644:Genetic Variation; D005838:Genotype; D007248:Infertility, Male / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D009865:Oocytes / Q000166:cytology*; D013075:Sperm Capacitation / Q000235:genetics*; D013081:Sperm Motility / Q000235:genetics; D013084:Sperm-Ovum Interactions / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D015044:Zona Pellucida / Q000378:metabolism; D056427:t-Complex Genome Region
D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C116196:PPP1R11 protein, human; D044767:Ubiquitin-Protein Ligases