A quantitative test for developmental neutrality of a transgenic lineage marker in mouse chimaeras.

The mouse transgene, provisionally designated TgN(Hbb-b1)83Clo, was produced by Dr C. Lo by pronuclear injection of the cloned beta-major globin gene and comprises a highly reiterated sequence that is readily detected by DNA in situ hybridization on histological sections. This fulfils many of the requirements of an ideal genetic cell marker and has been widely used for lineage studies with mouse chimaeras. However, it is not known whether it causes cell selection or influences developmental processes, such as cell mixing, in chimaeric tissues. In the present study, non-transgenic genetic markers (electrophoretic polymorphisms of glucose phosphate isomerase and differences in eye pigmentation) revealed no significant effect of the presence of hemizygous transgenic cells on the overall composition, size or gross morphology of 12 1/2 d chimaeric foetuses, placentas or extraembryonic membranes. Also, a previously described maternal genetic effect on the composition of chimaeric tissues occurred in the presence or absence of the transgene. These tests have demonstrated that hemizygous cells are not at a significant selective disadvantage, when incorporated into mouse aggregation chimaeras with non-transgenic cells. Further studies are needed to test whether homozygous transgenic cells are also selectively neutral and to test whether hemizygous or homozygous transgenic cells influence developmental processes, such as cell mixing, that were not tested.