SEX RATION DISTORTION AND THE PH-20 SPERM ANTIGEN

性别比例失调和 PH-20 精子抗原

• 批准号: 2456349
• 负责人: PATRICIA ANASTASIA DELEON
• 金额: $ 7.54万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-19 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2456349
• 关键词: cell adhesion molecules; cell age; cell fusion; chromosome translocation; developmental genetics; enzyme activity; fertilization; fluorescent in situ hybridization; gene expression; genetic regulation; hyaluronidase; laboratory mouse; male reproductive system disorder; molecular shape; northern blottings; sex chromosomes; sex determination; sperm; sperm motility; western blottings

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.

描述：（根据申请人的描述改编）长期目标 拟议的研究是为了了解 pH-20基因可能在小鼠的隔离和性别比扭曲中发挥作用 RB（6.16）或RB（6.15）易位的杂合子。 遗传和 分子方法将用于支持基因的候选性 精子中具有这些易位的功能障碍，尤其是那些易位 与X染色体。 具体来说，以下假设将是 测试：1。基于人和老鼠中的染色体同源性，鼠 pH-20基因地图到附近染色体6的近端区域 易位交界处，是功能障碍的位置候选者 在带有RB（6.16）或RB（6.15）易位的精子中可见。 ii。 这 pH-20 mRNA的表达水平及其编码蛋白在 纯合的男性，至少有一个基本的施肥一步改变了 与染色体正常的辅助小鼠相比，RB（6.16）或RB（6.15），并且 表达是在精子晚期发生的单倍体特异性。 iii。 分离和性别比失真，有利于xy zygotes， 带有C57BL/6J Y-chromosom的RB（6.16）或RB（6.15）载体 当易位分开时发生了变化：a）与a关联的y 更大，更圆的精子头，b）与头部相关的已删除y 有利于女性的异常和性别比扭曲。 iv。 拉紧 精子头的差异和精子年龄可能会影响 pH-20蛋白的定位。 V.精子特异性的产物 由Y染色体上的基因编码的转录本可能与 pH-20蛋白。 这项工作对我们对我们的理解具有巨大的影响 影响哺乳动物受精的因素，特别是对于人类 已知种族隔离失真已知RB（13; 14）和囊性存在 纤维化。 它还可以定义某些确定性的遗传原因 男性不育症或不育的类别是由异常引起的 精子 - 蛋的相互作用，可以进行筛查。