Redkar A A, Si Y, Twine S N, Pilder S H, Olds-Clarke P
Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Dev Biol. 2000 Oct 15;226(2):267-80. doi: 10.1006/dbio.2000.9870.
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.
t单倍型（t）是位于17号染色体近端的小鼠t复合区域另一种形式的近期进化衍生物。这种约占小鼠基因组1%的变异形式是改变众多对受精至关重要的精子功能的突变来源。携带两个t单倍型（t/t）的雄性总是不育的。t单倍型相对于野生型t复合区域（+）包含四个倒位，因此在涉及+/t杂合子的交配中，t通常作为一个单一单元传递。然而，已经获得了罕见的重组体，它们仅携带部分t基因型，并且仅表达一些t依赖的表型。在遗传杂交中使用这些部分t单倍型已导致两个主要的t雄性不育因子S1和S2分别大致定位在倒位1和倒位4内。由于不育可能由过多的精子缺陷导致，我们对携带S1或S2杂合或纯合或组合的小鼠精子的各种功能参数进行了详细研究。S1和S2都包含改变精子功能的突变，包括运动能力、获能、与透明带结合、与卵母细胞膜结合以及穿透无透明带的卵母细胞。因此，很明显这些因子中的每一个都包含多个导致不育的基因。此外，我们的结果表明，对于所检测的所有精子功能，S1中的基因与S2中的基因相互作用。然而，影响运动能力的S1和S2基因以纯粹相加的方式相互作用，而影响大多数其他精子特征的S1和S2基因以协同方式相互作用。此外，S1和S2在获能异常、精子 - 卵细胞膜结合以及无透明带卵母细胞穿透方面的协同模式几乎相同。这表明这三个缺陷是由每个不育因子内相同基因的突变引起的。这些发现不仅有助于将各种t单倍型精子缺陷与S1和S2的候选基因进行匹配，而且将有助于更全面地理解t单倍型雄性不育背后的细胞和遗传机制。
