SEX RATION DISTORTION AND THE PH-20 SPERM ANTIGEN

描述：(根据申请者的描述改编)长期目标 建议的研究的其中一个目的是了解 PH-20基因可能在小鼠性比分离和性别比扭曲中起作用 Rb(6.16)或Rb(6.15)易位为杂合子。遗传和 分子方法将被用来支持该基因的候选 携带这些易位的精子功能障碍，特别是那些 X染色体的基因。具体地说，以下假设将是 检测：1.基于人和小鼠的染色体同源性，小鼠 Ph-20基因定位于6号染色体近端区域 易位连接是功能障碍的一个位置候选 可见于携带Rb(6.16)或Rb(6.15)易位的精子。II. Ph-20mRNA及其编码蛋白的表达水平 受精过程中至少有一个基本步骤在纯合子男性身上发生了改变 Rb(6.16)或Rb(6.15)与染色体正常的共体鼠比较，以及 表达是单倍体特有的，发生在精子细胞的晚期。三. 分离和性别比扭曲，有利于XY受精卵 携带C57BL/6J Y染色体的Rb(6.16)或Rb(6.15)携带者可能是 当易位分离时改变：a)Y与 更大和更圆的精子头，以及b)与头相关的Y缺失 反常现象和性别比扭曲偏向女性。四、品系 精子头部形状和精子年龄的差异可能会影响 Ph-20蛋白的定位。V.精子细胞专一性的产物 Y染色体上的一个基因(S)编码的转录本(S)可能与 PH-20蛋白。这项工作对我们理解 影响哺乳动物受精的因素，特别是对人类来说 Rb(13；14)和囊状的偏析扭曲是已知的 纤维化症。它还可以定义某些潜在的遗传原因 男性不育或不育的类别，由#年的异常引起 精子-卵子的相互作用，可以进行筛选。

DESCRIPTION: (Adapted from applicant's description) The long-term objective of the proposed studies is to gain an understanding of the role that the ph-20 gene may play in the segregation and sex ratio distortions in mice heterozygous for the Rb(6.16) or Rb(6.15) translocation. Genetic and molecular approaches will be used to support the candidacy of the gene for the dysfunction in sperm bearing these translocations, particularly those with the X-chromosome. Specifically, the following hypotheses will be tested: 1. Based on chromosome homology in the human and mouse, the murine ph-20 gene maps to the proximal region of chromosome 6 near the translocation junction and is a positional candidate for the dysfunction seen in sperm bearing the Rb(6.16) or Rb(6.15) translocation. II. The level of expression of ph-20 mRNA and its encoded protein which performs at least one essential step in fertilization is altered in males homozygous for the Rb(6.16) or Rb(6.15) compared to chromosomally normal consomic mice, and expression is haploid specific occurring at the late spermatid stage. III. The segregation and sex ratio distortion, in favor of XY zygotes, in Rb(6.16) or Rb(6.15) carriers with the C57BL/6J Y-chromosome might be altered when the translocation segregates with: a) a Y associated with a larger and rounder sperm head, and b) a deleted Y associated with head anomalies and a sex ratio distortion in favor of females. IV. Strain differences in sperm head shape, and sperm age may influence the localization of the ph-20 protein. V. The product of a spermatid-specific transcript(s) encoded by a gene(s) on the Y chromosome may interact with the ph-20 protein. The work has enormous implications for our understanding of factors affecting mammalian fertilization, and particularly for humans where segregation distortion is known to exist for Rb(13;14) and for cystic fibrosis. It could also define the genetic causes underlying certain classes of male infertility or subfertility, resulting from anomalies in sperm-egg interactions, for which screening could be done.