CELL BIOLOGICAL AND BIOCHEMICAL STUDIES ON FUNCTION OF THE ter GENE IN PRIMORDIAL GERM CELL DEFICIENCY IN ter MUTANT MICE.

突变小鼠原始生殖细胞缺陷中 ter 基因功能的细胞生物学和生物化学研究。

• 批准号: 07680913
• 负责人: NOGUCHI Motoko
• 金额: $ 1.47万
• 依托单位: SHIZUOKA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07680913/
• 关键词: ter (teratoma) gene; Mouse embryo; Primordial germ cell; Germ-cell growth factor; Germ cell deficiency; Conditioned medium; ter congenic strain; Apoptosis; コンデイションドメディウム; terコンジェニック系統; 細胞培養; 細胞周期

Mutant strains having the ter (teratoma, Chr.18) mutation can serve as useful tools for studies of proliferation, survival and teratocarcinogenesis of primordial germ cells (PGC) in mice. Characteristics of the ter gene obtained are summarized below :1.The ter gene induces PGC deficiency from 8 days of gestation in ter/ter mice of the ter-congenic strains such as B6-+/ter, LTXBJ-+/ter and C3H-+/ter which we have established by introducing the ter gene from 129/Sv-+/ter mice onto the genetic backgrounds of B6, LTXBJ and C3H strains, respectively.2.Each ter genotype of each embryo of ter-congenic strains was identified by SSLP of the microsatellite markers near the ter locus.3.PGC deficiency in ter mutant testes is ascribed to their intratubular defect and +/+ gonocytes occurred apoptosis in reconstituted testes with ter testicular somatic cells, whereas they differentiated to spermatogenic cells in those with own somatic cells. These indicate that the ter gene may function in ter somatic cells.4.This type PGC-deficiency was not rescued by addition of several PGC growth factors in vitro and was induced by apoptosis in the G1 phase of PGC.5.PGC co-cultured with own somatic cells proliferated in conditioned medium (CM) of +/+ and +/ter somatic cells of fetal gonads, but they did not in terCM.+/+CM contained protein like substance supporting PGC survival, but terCM did not. Both +/+ and ter PGC isolated proliferated on the +/+ somatic cells, but they occurred apoptosis on the ter ones.6.It is concluded that a novel PGC growth factor (designated as TER Factor, TERF), both soluble type and membrane bounded type, supporting PGC survival may be produced by gonadal somatic cells and that it may be coded by the normal gene on the ter locus, and also that ter PGC are normal.

具有该突变的突变株可作为研究小鼠原始生殖细胞(PGC)增殖、存活和致畸的有用工具。所获得的TER基因的特点概括如下：1.将129/Sv-+/TER小鼠的TER基因导入B6-、LTXBJ-+/TER和C3H-+/TER三个品系的TER/TER小鼠中，TER基因可引起孕8天起的PGC缺陷。3.突变的睾丸PGC缺陷可归因于其管内缺陷，在含有睾丸体细胞的重组睾丸中+/+性细胞发生凋亡，而在具有自身体细胞的重组睾丸中，+/+性腺细胞分化为生精细胞。这说明TER基因可能在TER体细胞中起作用。4.PGC缺乏症在体外不能通过添加几种PGC生长因子来挽救，而是由G1期的细胞凋亡所诱导。5.PGC与自身体细胞在+/+和+/TER体细胞条件培养液(CM)中增殖，但在CM中没有。+/+CM含有支持PGC存活的蛋白质样物质，而TerCM没有。分离的+/+和TER PGC均在+/+体细胞上增殖，但在+/+体细胞上发生了凋亡。6.提示性腺体细胞可能产生一种支持PGC存活的新的PGC生长因子，命名为TER因子，既有可溶型又有膜结合型，可能是由TER基因编码的，且TER PGC是正常的。

项目成果

野口 基子: "腫瘍形成「生殖細胞-形態から分子へ」(岡田益吉・長濱嘉孝,編)" 共立出版, 17 (1996)

Motoko Noguchi：“肿瘤发生‘生殖细胞 - 从形态到分子’（Masukichi Okada 和 Yoshitaka Nagahama，编辑）” Kyoritsu Shuppan，17 (1996)

Noguchi, M.: "The ter mutation responsible for germ cell deficiency but not testicular nor ovarian teratocarcinogenesis in ter/ter congenic mice." Development Growth & Differentiation. 38. 59-69 (1996)

Noguchi, M.：“ter 突变导致了 ter/ter 同源小鼠的生殖细胞缺陷，但不是睾丸或卵巢畸胎癌的发生。”

Noguchi, M.et al.: "The ter mutation responsible for germ cell deficiency but not testicular nor ovarian terato-carcinogenesis in ter/ter congenic mice." Develop.Growth & Differ.38 (1). 59-69 (1996)

Noguchi, M.等人：“ter 突变导致了 ter/ter 同源小鼠的生殖细胞缺陷，但不是睾丸或卵巢畸胎癌的发生。”

Sakurai, T.: "The ter mutation first causes primordial germ cell deficiency in ter/ter mouse embryos at 8 days of gestation." Development Growth & Differentiation. 37. 293-302 (1995)

Sakurai, T.：“ter 突变首先导致 ter/ter 小鼠胚胎在妊娠 8 天时出现原始生殖细胞缺陷。”

Noguchi,M.: "A novel primordial germ cell growth factor,TER Factor,produced by mouse testicular somatic cells." J.Reprod.Develop.43(in press). (1997)

Noguchi,M.：“一种新型原始生殖细胞生长因子，TER 因子，由小鼠睾丸体细胞产生。”