Siracusa L D, Chapman V M, Bennett K L, Hastie N D, Pietras D F, Rossant J
J Embryol Exp Morphol. 1983 Feb;73:163-78.
Mammalian chimaeras have proved useful for investigating early steps in embryonic development. However, a complete clonal analysis of cell lineages has been limited by the lack of a marker which is ubiquitous and can distinguish parental cell types in situ. We have developed a cell marker system which fulfils these criteria. Chimaeric mice were successfully produced from two mouse species which possess sufficient genetic differences to allow unequivocal identification of parental cell types. DNA-DNA in situ hybridization with cloned, species-specific sequences was performed to distinguish the parental cell types. We have identified a cloned, Mus musculus satellite DNA sequence which shows hybridization differences between Mus musculus and Mus caroli DNA. This clone was used a a probe in in situ hybridizations to bone marrow chromosomes from Mus musculus, Mus caroli, and an interspecific F1 hybrid. The clone could qualitatively distinguish Mus musculus from Mus caroli chromosomes after in situ hybridization, even when they were derived from the same F1 hybrid cell. Quantitation of this hybridization to interphase nuclei from bone marrow spreads indicates that the probe can successfully distinguish Mus musculus from Mus caroli cells and can determine the percentage contribution of Mus musculus in mixtures of bone marrow cells of these species and in chimaeric bone marrow cell preparations.
事实证明,哺乳动物嵌合体有助于研究胚胎发育的早期阶段。然而,由于缺乏一种在体内普遍存在且能区分亲代细胞类型的标记物,对细胞谱系进行完整的克隆分析受到了限制。我们开发了一种满足这些标准的细胞标记系统。利用两种具有足够遗传差异以便明确鉴定亲代细胞类型的小鼠成功培育出了嵌合小鼠。通过与克隆的物种特异性序列进行DNA-DNA原位杂交来区分亲代细胞类型。我们鉴定出了一个克隆的小家鼠卫星DNA序列,该序列在小家鼠和野小鼠的DNA之间表现出杂交差异。这个克隆被用作原位杂交的探针,用于小家鼠、野小鼠以及种间F1杂种的骨髓染色体。原位杂交后,该克隆能够从定性上区分小家鼠和野小鼠的染色体,即使它们来自同一个F1杂种细胞。对骨髓涂片间期核的这种杂交进行定量分析表明,该探针能够成功区分小家鼠和野小鼠细胞,并且能够确定小家鼠在这些物种的骨髓细胞混合物以及嵌合骨髓细胞制剂中的百分比贡献。