GERM CELL-SPECIFIC MOLECULES OF SPERMATOZOA

精子生殖细胞特异性分子

• 批准号: 3841149
• 负责人: E M EDDY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3841149
• 关键词: Sertoli cells; acrosin; acrosome; carbohydrate receptor; cell cell interaction; developmental genetics; gene expression; genetic models; genetically modified animals; germ cells; glyceraldehyde 3 phosphate dehydrogenase; glycolysis; hexokinase; laboratory mouse; mannose; meiosis; nucleic acid hybridization; receptor binding; regulatory gene; site directed mutagenesis; sperm; spermatogenesis

Gene expression during spermatogenesis in mammals is being examined to define intrinsic and extrinsic mechanisms regulating development and function of male gametes. Genes being studied are expressed uniquely in spermatogenic cells and/or during specific stages of their development. The code for germ cell-specific isoforms of known proteins and include genes for glycolytic enzymes and proteins involved in cell-cell interaction. For example, cDNAs isolated hybridize with RNAs for glyceraldehyde 3-phosphate dehydrogenase (Gapd-s) and hexokinase expressed only in spermatogenic cells. The Gapd-s gene is expressed after meiosis in haploid spermatids, while expression of the hexokinase gene begins during meiosis in pachytene spermatocytes. Glucose is toxic to isolated spermatids but is required by spermatozoa for in vitro fertilization, indicating that unique regulatory processes occur for glycolysis in spermatogenic cells. In addition, mannose 6-phosphate (M6P) receptors have been identified on spermatogenic cells and shown to bind M6P-bearing ligands produced by Sertoli cells. Multiple transcripts for the cation- dependent M6P receptor in germ cells include 1.2 and 1.4 kb mRNAs not found in somatic cells. They probably arise from alternate polyadenylation signals, one being used in pachytene spermatocytes and the other in spermatids. Transgenic mice have been produced to examine the role of M6P receptors in targeting of acrosin, a sperm-specific serine protease, to the acrosome. Targeted mutations are also being used to knock out the acrosin gene to examine germ cell development and sperm function when there is a mutation in this gene. These studies also serve as models for the effects of gene mutations in humans caused by environmental agents that can be transmitted through the father to the next generation.

哺乳动物精子发生过程中的基因表达正在被研究， 确定调节发育的内在和外在机制， 雄配子的功能。 正在研究的基因在细胞中独特表达 生精细胞和/或在其发育的特定阶段。 已知蛋白质的生殖细胞特异性同种型的编码，包括 参与细胞间糖酵解酶和蛋白质的基因 互动 例如，分离的cDNA与RNA杂交， 甘油醛3-磷酸脱氢酶（Gapd-s）和己糖激酶表达 只存在于生精细胞中。 Gapd-s基因在减数分裂后表达， 单倍体精子细胞，而己糖激酶基因的表达开始于 粗线期精母细胞减数分裂。 葡萄糖对分离的 精子细胞，但是精子体外受精所需要的， 表明糖酵解发生独特的调节过程， 生精细胞 此外，甘露糖6-磷酸（M6 P）受体具有 在生精细胞上鉴定，并显示与携带M6 P的 支持细胞产生的配体。 多个阳离子的转录本- 生殖细胞中依赖性M6 P受体包括未发现的1.2和1.4 kb mRNA 在体细胞中。 它们可能是由交替的多聚腺苷酸化引起的 信号，一个用于粗线期精母细胞，另一个用于 精子细胞 已经产生转基因小鼠来检查M6 P的作用。 受体在靶向顶体蛋白酶，精子特异性丝氨酸蛋白酶， 顶体 靶向突变也被用来敲除顶体酶 基因检查生殖细胞发育和精子功能时，有一个 这个基因的突变。 这些研究也作为模型的影响， 由环境因素引起的人类基因突变， 通过父亲传给下一代。