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Genotypically unbalanced diploid ↔ diploid foetal mouse chimaeras: possible relevance to human confined mosaicism

Published online by Cambridge University Press:  14 April 2009

John D. West*
Affiliation:
Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, U.K.
Jean H. Flockhart
Affiliation:
Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, U.K.
*
* Corresponding author.
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Two series of mouse chimaeras were produced by aggregating pairs of eight-cell embryos that differed at the Gpi-1s locus, encoding glucose phosphate isomerase (GPI-1); the paired embryos were respectively homozygous Gpi-1sa/Gpi-1sa and Gpi-1sb/Gpi-1sb. Chimaeric blastocysts were transferred to pseudopregnant females, that were homozygous Gpi-1se/Gpi-1se and produced only GPI-1 C enzyme. Quantitative electrophoresis of GPI-1 was used to estimate the contribution of each embryo (GPI-1 A and GPI-1B enzyme activity) to the foetus, placenta and other extraembryonic tissues of 12½ day chimaericconceptuses. For both series of chimaeras, the distributions of %GPI-1A in different tissues were classified as (1) balanced and typical, (2) balanced but atypical or (3) unbalanced. One series of chimaeras was clearly unbalanced, so that the cells derived from the (C57BL × CBA/Ca)F2 embryo (Gpi-1sb/Gpi-1sb) predominated over those derived from the BALB/c inbred strain (Gpi-1sa/Gpi-1sa) in most foetuses. Two significant observations were made concerning this unbalanced series. Firstly, the mean composition of the placenta and other extraembryonic tissues was similar to that in the foetus i.e. also unbalanced with (C57BL × CBA/Ca)F2 (abbreviated to BF2) cells predominating. Secondly, despite this generalizeddeficiency of BALB/c cells, there were differences in the frequency of non-chimaeric tissues between different developmental lineages. In 20/34 chimaeric conceptuses in the unbalanced series only BF2 cells were detected in the foetus, whereas both BF2 and BALB/c cells were present in at least one of the extraembryonic tissues. This group of chimaeras, therefore, shows some similarities to human confined mosaicism. Although chimaerism occurred more often in the primitive endoderm (hypoblast) lineage (yolk sac endoderm and parietal endoderm) than in the placenta, this may also be the case in human mosaics. The mosaic status of the human yolk sac endoderm is usually unknown so it is possible that mosaicism often occurs in the yolk sac endoderm as well as the trophectoderm in human ‘confined placental mosaicism’. The uniformly unbalanced phenotype seen in the mouse chimaeras may be a result of generalized cell selection against BALB/c cells in all tissues. As an alternative explanation, we propose that most of the BALB/c cells in the blastocyst are allocated to the mural trophectoderm, which has a limited mitotic potential and so contributes little to the mid-gestation conceptus. Further work is required to test these possibilities.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1994

References

Canadian collaborative CVS-amniocentesis clinical trial group. (1989). Multicentre randomised clinical trial of chorion villus sampling and amniocentesis. Lancet i, 16.Google Scholar
Copp, A. J. (1978). Interaction between inner cell mass and trophectoderm of the mouse blastocyst. I. A study of cellular proliferation. Journal of Embryology and Experimental Morphology 48, 109125.Google Scholar
Copp, A. J. (1979). Interaction between inner cell mass and trophectoderm of the mouse blastocyst. II. The fate of the polar trophectoderm. Journal of Embryology and Experimental Morphology 51, 109120.Google ScholarPubMed
Crane, J. P. & Cheung, J. P. (1988). An embryogenetic model to explain cytogenetic inconsistencies observed in chorionic villus versus fetal tissue. Prenatal Diagnosis 8, 119129.CrossRefGoogle Scholar
Cruz, Y. P. & Pederson, R. A. (1985). Cell fate in the polar trophectoderm of mouse blastocysts as studied by microinjection of cell lineage tracers. Developmental Biology 112, 7383.Google Scholar
Ford, C. E. (1969). Mosaics and chimaeras. British Medical Bulletin 25, 104109.Google Scholar
Gardner, R. L. & Papaioannou, V. E. (1975). Differentiation in the trophectoderm and inner cell mass. In The Early Development of Mammals (ed. Balls, M. and Wild, A. E.), pp. 107132. Cambridge: Cambridge University Press.Google Scholar
Handyside, A. H. (1978). Time of commitment of inside cells isolated from preimplantation mouse embryos. Journal of Embryology and Experimental Morphology 45, 3753.Google ScholarPubMed
James, R., Flockhart, J. H., Keighren, M. & West, J. D. (1993). Quantitative analysis of midgestation mouse aggregation chimaeras: non-random composition of the placenta. Roux's Archives of Developmental Biology 202, 296305.CrossRefGoogle ScholarPubMed
Kalousek, D. K. (1990). Confined placental mosaicism and intrauterine development. Pediatric Pathology 10, 6977.CrossRefGoogle ScholarPubMed
Kalousek, D. K. & Dill, F. J. (1983). Chromosome mosaicism confined to the placenta in human conceptions. Science 221, 665667.Google Scholar
Levak-Svajger, B., Levak-Svajger, A. & Skreb, N. (1969). Separation of germ layers in presomite rat embryos. Experientia 25, 13111312.CrossRefGoogle Scholar
Luckett, W. P. (1978). Origin and differentiation of the yolk sac and extraembryonic mesoderm in presomite human and rhesus monkey embryos. American Journal of Anatomy 152, 5998.CrossRefGoogle ScholarPubMed
McLaren, A. (1976). Mammalian Chimaeras. Cambridge: Cambridge University Press.Google Scholar
McLaren, A. & Buehr, M. (1990). Development of mouse germ cells in cultures of fetal gonads. Cell Differentiation and Development 31, 185195.CrossRefGoogle ScholarPubMed
McLaren, A. & Michie, D. (1956). Studies on the transfer of fertilized mouse eggs to uterine foster mothers. I. Factors affecting the implantation and survival of native and transferred eggs. Journal of Experimental Biology 33, 394416.CrossRefGoogle Scholar
Mintz, B. (1962). Formation of genotypically mosaic mouse embryos. American Zoologist 2, 432 (abstract 310).Google Scholar
Mintz, B., Gearhart, J. D. & Guymont, A. G. (1973). Phytohemagglutinin-mediated blastomere aggregation and development of allophenic mice. Developmental Biology 31, 195199.CrossRefGoogle ScholarPubMed
MRC working party on the evaluation of chorion villus sampling (1991). Medical Research Council European trial of chorion villus sampling. Lancet 337, 14911499.CrossRefGoogle Scholar
Mullen, R. J. & Whitten, W. K. (1971). Relationship of genotype and degree of coat colour to sex ratios and gametogenesis in chimaeric mice. Journal of Experimental Zoology 178, 165176.CrossRefGoogle Scholar
Nicolson, G. L., Yanagamachi, R. & Yanagamachi, H. (1975). Ultrastructural localization of lectin binding sites of the zonae pellucidae and plasma membranes of mammalian eggs. Journal of Cell Biology 66, 263274.CrossRefGoogle ScholarPubMed
Palmer, S. J. & Burgoyne, P. S. (1991). The Mus musculus domesticus Tdy allele acts later than the Mus musculus musculus Tdy allele: a basis for XY sex reversal in C57BL/6-Ypos mice. Development 113, 709714.CrossRefGoogle Scholar
Pratt, H. P. M. (1987). Isolation, culture and manipulation of pre-implantation mouse embryos. In Mammalian Development: A Practical Approach (Ed. Monk, M.), pp. 2942. Oxford: IRL Press.Google Scholar
Quinn, P., Barros, C. & Whittingham, D. G. (1982) Preservation of hamster oocytes to assay the fertilizing capacity of human spermatozoa. Journal of Reproduction and Fertility 66, 161168.CrossRefGoogle ScholarPubMed
Rossant, J. & Croy, B. A. (1985). Genetic identification of the tissue of origin of cellular populations within the mouse placenta. Journal of Embryology and Experimental Morphology 86, 177189.Google Scholar
Tarkowski, A. K. (1961). Mouse chimaeras developed from fused eggs. Nature 190, 857–60.Google Scholar
West, J. D. & Green, J. F. (1983). The transition from oocyte-coded to embryo-coded glucose phosphate iso-merase in the early mouse embryo. Journal of Embryology and Experimental Morphology 78, 127140.Google ScholarPubMed
West, J. D., Leask, R. & Green, J. F. (1986). Quantification of the transition from oocyte-coded to embryo-coded glucose phosphate isomerase in mouse embryos. Journal of Embryology and Experimental Morphology 97, 225237.Google ScholarPubMed
Whittingham, D. G. (1971). Culture of mouse ova. Journal of Reproduction and Fertility (Suppl.) 14, 721.Google ScholarPubMed