Rossant J, Croy B A, Clark D A, Chapman V M
J Exp Zool. 1983 Nov;228(2):223-33. doi: 10.1002/jez.1402280208.
Interspecific hybrids and chimeras in mammals provide unique tools for investigating problems in genetics and embryology, because of the degree of disparity between the two component genotypes. We have attempted to produce hybrids and chimeras between Mus musculus, the laboratory mouse, and Mus caroli, a wild species of mouse from Southeast Asia. M. musculus and M. caroli do not normally interbreed, although sterile hybrids can be produced at a low rate by artificial insemination. Extrinsic problems of genotypic incompatibility between the fetus and the maternal environment seem to be involved in poor hybrid survival, since M. caroli blastocysts also die when transferred to the M. musculus uterus. Death is associated with the generation of maternal T-cells which are cytotoxic to M. caroli target cells in vitro. It is not yet clear whether this immune response is the primary cause of death or is secondary to breakdown of some other components of the fetal-maternal interaction. It is clear, however, that it is the trophoblast layer that mediates survival or death of the foreign embryonic cells in the M. musculus juterus, since M. caroli inner cell mass cells can survive to term after injection into M. musculus blastocysts: Viable interspecific chimeras result. Even more convincing evidence is provided by the production of viable M. caroli offspring by trophoblast vesicle reconstitution using trophoblast of M. musculus genotype and inner-cell mass of M. caroli type. Studies of properties of isolated trophoblast tissues have indicated that M. caroli trophoblast may differ from M. musculus in both its antigenic and immunosuppressive properties. Elucidation of trophoblast-uterine interactions in these various interspecific pregnancies is being aided by the development of an in situ marker system, which can distinguish cells of the two species in sectioned material by in situ hybridization with a M. musculus satellite DNA probe. This same marker is also proving a very powerful tool for analyzing cell lineage development in chimeras.
由于两种组成基因型之间的差异程度,哺乳动物中的种间杂种和嵌合体为研究遗传学和胚胎学问题提供了独特的工具。我们试图在实验小鼠小家鼠(Mus musculus)和来自东南亚的野生小鼠罗氏鼠(Mus caroli)之间产生杂种和嵌合体。小家鼠和罗氏鼠通常不会杂交,尽管通过人工授精可以以较低的比率产生不育杂种。胎儿与母体环境之间基因型不相容的外在问题似乎与杂种存活率低有关,因为将罗氏鼠囊胚转移到小家鼠子宫中时也会死亡。死亡与母体T细胞的产生有关,这些T细胞在体外对罗氏鼠靶细胞具有细胞毒性。目前尚不清楚这种免疫反应是死亡的主要原因还是胎儿 - 母体相互作用的其他一些成分破坏的继发结果。然而,很明显,是滋养层介导了小家鼠子宫中外来胚胎细胞的存活或死亡,因为将罗氏鼠内细胞团细胞注射到小家鼠囊胚中后可以存活至足月:产生了可行的种间嵌合体。使用小家鼠基因型的滋养层和罗氏鼠型的内细胞团通过滋养层囊泡重建产生可行的罗氏鼠后代提供了更有说服力的证据。对分离的滋养层组织特性的研究表明,罗氏鼠滋养层在抗原性和免疫抑制特性方面可能与小家鼠不同。一种原位标记系统的开发有助于阐明这些各种种间妊娠中滋养层与子宫的相互作用,该系统可以通过与小家鼠卫星DNA探针的原位杂交在切片材料中区分两种物种的细胞。同样的标记也被证明是分析嵌合体中细胞谱系发育的非常强大的工具。