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Evaluation of triploiddiploid and trisomy-3diploid mouse chimeras as models for investigating how lineage restriction occurs in confined placental mosaicism

Genes and Development Group, Division of Reproductive and Developmental Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, Scotland, UK

Correspondence should be addressed to J D West; Email: john.west{at}ed.ac.uk

Human confined placental mosaicism (CPM), where the placental trophoblast is mosaic for a chromosome abnormality but the fetus is chromosomally normal, can cause problems for prenatal diagnosis, but its causes are poorly understood. Tetraploiddiploid chimeras provide a model for the development of one type of CPM, but animal models for other types of restricted mosaicism are needed. The objective of the present study was to evaluate triploiddiploid and trisomy-3diploid chimeric mouse conceptuses as new models for investigating the development of restricted mosaicism. Novel stocks of mice were generated to produce triploid and trisomy-3 embryos that could be identified by DNA in situ hybridisation to a chromosome 3 transgenic marker. Triploiddiploid and trisomy-3diploid mouse chimeras were produced byembryo aggregation, and the contribution of triploid or trisomy-3 cells was analysed in the fetus and extraembryonic tissues. Only two trisomy-3diploid chimeras were analysed but trisomy-3 cells contributed well to all lineages, so these chimeras did not show restricted mosaicism. In contrast, triploid cells usually contributed poorly to all lineages in the ten 3n2n chimeras analysed. They contributed more to the primitive endoderm derivatives than other lineages and were present in the primitive endoderm derivatives of all ten chimeras, but excluded from fetuses and trophectoderm derivatives in some cases. This pattern of restricted mosaicism differs from that reported for tetraploid cells in tetraploiddiploid chimeras, and triploiddiploid chimeras may provide a useful model for the development of some types of restricted mosaicism in human conceptuses.