Identification of Gasz, an evolutionarily conserved gene expressed exclusively in germ cells and encoding a protein with four ankyrin repeats, a sterile-alpha motif, and a basic leucine zipper.
Identification of Gasz, an evolutionarily conserved gene expressed exclusively in germ cells and encoding a protein with four ankyrin repeats, a sterile-alpha motif, and a basic leucine zipper.
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DOI：
10.1210/mend.16.6.0864
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发表时间：
2002-06
影响因子：
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通讯作者：
Wei Yan;A. Rajkovic;M. Viveiros;K. Burns;J. Eppig;M. Matzuk
中科院分区：
文献类型：
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作者：
Wei Yan;A. Rajkovic;M. Viveiros;K. Burns;J. Eppig;M. Matzuk
为了发现不孕的原因和潜在的避孕目标，我们使用计算机减法和基因组数据库挖掘来识别具有生殖细胞特异性表达的保守基因。计算机减法鉴定出仅存在于新生小鼠卵巢文库中的表达序列标签（EST）。与该 EST 相对应的全长 cDNA 序列编码一种新型蛋白质，其中包含四个锚蛋白 (ANK) 重复序列、一个无菌 α 基序 (SAM) 和一个推定的碱性亮氨酸拉链 (bZIP) 结构域。 Northern 印迹和半定量 RT-PCR 分析表明 mRNA 只在小鼠睾丸和卵巢中表达。通过对睾丸中的粗线期精母细胞和卵巢中的卵母细胞进行原位杂交来定位表达位点。免疫组织化学表明，这种新蛋白定位于粗线期精母细胞和早期精子细胞、卵子发生各个阶段的卵母细胞以及早期植入前胚胎的细胞质。基于其生殖细胞特异性表达以及 ANK、SAM 和碱性亮氨酸拉链结构域的存在，我们将这种新型蛋白命名为 GASZ。小鼠 Gasz 基因由 13 个外显子组成，全长 60 kb，位于 6 号染色体上 Wnt2 和囊性纤维化跨膜电导调节 (Cftr) 基因之间。通过基因组数据库挖掘，在大鼠、牛、狒狒、黑猩猩和人类中鉴定出了编码 GASZ 的直系同源基因。系统发育分析表明，GASZ 蛋白在这些物种中高度保守。人类和小鼠 GASZ 蛋白具有 85.3% 的氨基酸同一性，而人类和黑猩猩 GASZ 蛋白的 475 个氨基酸中仅存在 3 个不同。在人类中，GASZ 基因位于 7 号染色体上，同样由 13 个外显子组成。由于 ANK 重复序列和 SAM 结构域都充当蛋白质-蛋白质相互作用模块，在某些系统中介导信号转导级联，因此 GASZ 可能代表重要的细胞质信号转导器，在男性和女性生殖细胞成熟期间以及植入前胚胎发生期间介导蛋白质-蛋白质相互作用。
To discover causes of infertility and potential contraceptive targets, we used in silico subtraction and genomic database mining to identify conserved genes with germ cell-specific expression. In silico subtraction identified an expressed sequence tag (EST) present exclusively in a newborn mouse ovary library. The full-length cDNA sequence corresponding to this EST encodes a novel protein containing four ankyrin (ANK) repeats, a sterile-alpha motif (SAM), and a putative basic leucine zipper (bZIP) domain. Northern blot and semiquantitative RT-PCR analyses demonstrated that the mRNA is exclusively expressed in the mouse testis and ovary. The expression sites were localized by in situ hybridization to pachytene spermatocytes in the testis and oocytes in the ovary. Immunohistochemistry showed that the novel protein is localized to the cytoplasm in pachytene spermatocytes and early spermatids, oocytes at all stages of oogenesis, and in early preimplantation embryos. Based on its germ cell-specific expression and the presence of ANK, SAM, and basic leucine zipper domains, we have termed this novel protein GASZ. The mouse Gasz gene, which consists of 13 exons and spans 60 kb, is located on chromosome 6 between the Wnt2 and cystic fibrosis transmembrane conductance regulator (Cftr) genes. Using genomic database mining, orthologous genes encoding GASZ were identified in the rat, cow, baboon, chimpanzee, and human. Phylogenetic analyses reveal that the GASZ proteins are highly conserved among these species. Human and mouse GASZ proteins share 85.3% amino acid identity, and human and chimpanzee GASZ proteins differ by only 3 out of 475 amino acids. In humans, the GASZ gene resides on chromosome 7 and is similarly composed of 13 exons. Because both ANK repeats and the SAM domain function as protein-protein interaction modules that mediate signal transduction cascades in some systems, GASZ may represent an important cytoplasmic signal transducer that mediates protein-protein interactions during germ cell maturation in both males and females and during preimplantation embryogenesis.