DEVELOPMENTAL BIOLOGICAL STUDIES ON FUNCTION OF THE ter GENEIN DEFICIENCY AND TERATOCARCINOGENESIS OF PRIMORDIAL GERM CELLS IN ter MUTANT MICE

1. 该畸胎瘤突变导致129/Sv-ter菌株的ter/ter小鼠从胎儿期到成年期生殖细胞缺乏，以及我们分别将129/Sv-ter小鼠的ter基因引入B6、LTXBJ和C3H/HeJ-ter （C3H-ter）的ter-同源菌株C57BL/6J-ter（B6-ter）、LTXBJ-ter和C3H/HeJ-ter （C3H-ter）。在遗传背景为129/ v-ter的菌株中，ter基因诱导自发性睾丸畸胎瘤的发生率也很高，但在其同源菌株中没有实验性睾丸和卵巢畸胎瘤。结果表明，该ter基因座与Grl-1基因座在Chr 18上的定位关系密切，且Grl-1基因的微卫星DNA的SSLP （Simple Sequence Length Polymorphisms）可以对每个胚胎或成体的ter基因型进行鉴定。利用SSLP基因分型对其同源胚胎进行组织化学研究，发现在妊娠第8天，ter基因首先引起突变胚胎的原始生殖细胞缺陷。在ter基因菌株中，由分离的胎儿睾丸中+/+和+/ter的性腺细胞和ter/ter的体细胞重组而成的睾丸发生生殖细胞缺乏，而在正常的性腺细胞和体细胞中发生精子发生，这表明ter基因可能通过影响胎儿ter/ter睾丸中的体细胞而引起生殖细胞缺乏。LTXBJ细胞与129/Sv-ter体细胞重组的胎儿睾丸中可诱发畸胎瘤，而相互重组的胎儿睾丸中未发生肿瘤，提示具有129/Sv-ter遗传背景的胎儿睾丸体细胞可能在睾丸畸胎瘤发生中起关键作用。

1. The ter (teratoma) mutation caused germ cell deficiency from fetal stages to adulthood in ter/ter mice of the strain 129/Sv-ter and the ter-congenic strains, C57BL/6J-ter(B6-ter), LTXBJ-ter, and C3H/HeJ-ter (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, respsctively. The ter gene induced also a high incidence of spontaneous testicular teratomas in the genetic background of 129/Sv-ter, but not experimental testicular nor ovarian teratomas in ter congenic strains.2. It was found that the ter locus maps closely to Grl-1 locus on Chr. 18 and that cach ter genotype of each embryo or adult can be identified by SSLP (Simple Sequence Length Polymorphisms) of the microsatellite DNA of the Grl-1 gene.3. By histochemical studies on ter congenic embryos ter-genotyped by SSLP,it was showed that the ter gene first causes primordial germ cell deficiency in ter mutant embryos at 8 days of gestation.4. Germ cell deficiency occurred in testes reconstituted from reaggregates produced from+/+and+/ter gonocytes and ter/ter somatic cells from dissociated fetal testes in the ter congenic strain, whereas spermatogenesis did in those from normal gonocytes and somatic cells, suggesting that the ter gene may cause germ cell deficiency by affecting somatic cells in fetal ter/ter testes.5. Testicular teratomas were induced in fetal testes reconstituted between LTXBJ gonocytes and 129/Sv-ter somatic cells, whereas no tumors were in those recombined reciprocally, showing that somatic cells from fetal testes having 129/Sv-ter genetic background may play a key role in testicular teratocarcinogenesis.