GENE EXPRESSION IN SPERMATOGENIC CELLS

这些研究的长期目标是确定 调节男性生殖细胞的发育。我们正在与之接洽 通过鉴定在雄性生殖细胞中特异表达的基因 并在雄性生殖细胞的特定阶段上调 发展。这些基因被称为沙文主义基因，因为男性生殖细胞 细胞对它们的表达怀有强烈的偏见。它们包括细菌 细胞同源基因、独特基因和表达独特基因 成绩单。生殖细胞同源基因仅在 生精细胞，但与其他表达在 体细胞。其中之一是甘油醛3-磷酸脱氢酶。 (Gapd-S)，可能在男性生育和生殖方面起重要作用 毒物学。精子中的GAPD-S酶处于“关闭”状态，而在精子中处于“开启”状态 并在调节所需的三磷酸腺苷的生成方面起着关键作用 受精。GAPD-S和GAPD-S蛋白的表达 已确定转录所需的最小启动子区域 在转基因小鼠中已经被发现，并且由一种 Gapd-S基因的敲除正在确定中。研究也在进行 正在进行的是在三个独特的基因中产生靶向突变 仅在生精细胞中表达，缺乏体细胞亚型。 这些基因编码的蛋白质被认为在精子-卵子中起着关键作用。 结合(受精素β)、精子细胞核凝聚(鱼精蛋白1)、 和鞭毛结构完整性(Fscl)。受精素β蛋白是 一种含有金属蛋白酶和去整合素的精子表面成分 结构域，并与鸡蛋上的α1β6整合素特异性结合 浮出水面。鱼精蛋白1是一种取代组蛋白的高度碱性蛋白质 在DNA在形成的精子头中紧凑的过程中。FSCL是一个专业 精子鞭毛的细胞骨架成分。基因突变 预计会扰乱精子形成或受精 在纯合子雄性小鼠中。预测的表型类似于 在一些不育男性身上观察到的情况，结果将是 对了解精子的发育和功能以及 以确定这些基因突变在人类中的可能作用 不孕不育。

The long-term goal of these studies is to determine the mechanisms that regulate development of germ cells in the male. This is being approached by identifying genes that are expressed specifically in male germ cells and are up-regulated during particular phases of male germ cell development. These are referred to as chauvinist genes because male germ cells favor their expression with strong prejudice. They include germ cell homologue genes, unique genes, and genes expressing unique transcripts. Germ cell homologue genes are expressed only in spermatogenic cells, but are closely related to other genes expressed in somatic cells. One of these is glyceraldehyde 3-phosphate dehydrogenase (Gapd-s), likely to be important in male fertility and reproductive toxicology. The GAPD-S enzyme is "off" in spermatids and "on" in sperm and has a key role in regulating the generation of ATP required for fertilization. The expression of the Gapd-s mRNA and GAPD-S protein have been determined, the minimum promoter region required for transcription in transgenic mice has been identified, and the phenotype produced by a knockout of the Gapd-s gene is being determined. Studies are also underway to produce targeted mutations in three unique genes that are expressed only in spermatogenic cells and lack somatic cell isoforms. These genes encode proteins believed to have critical roles in sperm-egg binding (fertilin beta), spermatid nuclear condensation (protamine 1), and flagellar structural integrity (Fscl). The fertilin beta protein is a sperm surface component that has metalloprotease and disintegrin domains, and binds specifically to alpha1beta6 integrin on the egg surface. Protamine 1 is a highly basic protein that replaces histones during the compaction of DNA in the forming sperm head. Fscl is a major cytoskeletal component of the sperm flagellum. Mutations in the genes are expected to produce disruption of sperm formation or fertilization in homozygous male mice. The predicted phenotypes are similar to conditions observed in some infertile men and the results will be valuable both for understanding the development and function of sperm and for determining the possible roles of mutations in these genes in human infertility.