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 建议的研究是为了了解的作用， ph-20基因可能在小鼠分离和性比畸变中起作用 Rb（6.16）或Rb（6.15）易位杂合。 遗传和 分子方法将用于支持候选基因， 携带这些易位的精子功能障碍，特别是那些 有X染色体 具体而言，以下假设将 测试：1. 基于人类和小鼠的染色体同源性， ph-20基因定位于6号染色体的近端区域， 易位连接，并且是功能障碍的位置候选者。 见于携带Rb（6.16）或Rb（6.15）易位的精子。 二. 的 pH-20 mRNA及其编码蛋白的表达水平， 在受精过程中，至少有一个重要步骤在纯合的雄性中发生了改变， Rb（6.16）或Rb（6.15）与染色体正常的同源小鼠相比，和 表达是单倍体特异性的，发生在精子细胞晚期。 三. 分离和性别比例的扭曲，有利于XY合子，在 Rb（6.16）或Rb（6.15）携带者与C57 BL/6 J Y染色体可能是 当易位分离时改变：a）Y与 更大更圆的精子头部，和B）与头部相关的缺失的Y 异常和性别比例扭曲有利于女性。 四. 应变 精子头部形状和精子年龄的差异可能会影响精子的发育。 pH-20蛋白的定位。 V.精细胞特异性 由Y染色体上的基因编码的转录物可以与Y染色体上的基因相互作用。 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， 已知Rb（13;14）和囊性Rb（13;14）存在分离畸变。 纤维化 它还可以确定某些疾病背后的遗传原因 男性不育或生育力低下的类别，由于异常， 精子与卵子的相互作用，可以进行筛选。