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

Published online by Cambridge University Press:  14 April 2009

John D. West ,
Margaret A. Keighren  and
Jean H. Flockhart
John D. West*
Affiliation:
Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, UK
Margaret A. Keighren
Affiliation:
Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, UK
Jean H. Flockhart
Affiliation:
Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, UK
*
* Corresponding author: Dr John D. West, Department of Obstetrics and Gynaecology, university of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, UK. Tel. 0131-229-2575; Fax. 0131-229-2408; Email: John.D.West@ed.ac.uk.
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The mouse transgene, provisionally designated TgN(Hbb-b1)83Clo, was produced by Dr C. Lo by pronuclear injection of the cloned ß-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, nontransgenic 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 12½ 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 aggregationchimaeras 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.

Type
Research Article
Information
Genetics Research , Volume 67 , Issue 2 , April 1996 , pp. 135 - 146
Copyright
Copyright © Cambridge University Press 1996

References

Boland, N. I. & Gosden, R. G. (1994). Clonal analysis of chimaeric mouse ovaries using DNA in situ hybridization. Journal of Reproduction and Fertility 100, 203–210.CrossRefGoogle ScholarPubMed
Everett, C. A., Keighren, M., & West, J. D. (1994). New transgenic Robertsonian strain. Mouse Genome 92, 668.Google Scholar
James, R., Flockhart, J. H., Keighren, M. & West, J. D. (1993). Quantitative analysis of mid-gestation mouse aggregation chimaeras: non-random composition of the placenta. Roux's Archives of Developmental Biology 202, 296–305.CrossRefGoogle ScholarPubMed
James, R. M., Klerkx, A. H. E. M., Keighren, M., Flockhart, J. H. & West, J. D. (1995). Restricted distribution of tetraploid cells in mouse tetraploid ↔ diploid chimaeras. Developmental Biology 167, 213–226.CrossRefGoogle ScholarPubMed
Katsumata, M. & Lo, C. W. (1988). Organization of chromosomes in the mouse nucleus: analysis by in situ hybridization. Journal of Cell Science 90, 193–199.CrossRefGoogle ScholarPubMed
Keighren, M. & West, J. D. (1993). Analysis of cell ploidy in histological sections of mouse tissues by DNA—DNA in situ hybridization with digoxygenin-labelled probes. Histochemical Journal 25, 30–44.CrossRefGoogle Scholar
Keighren, M. & West, J. D. (1994). Two new partially congenic transgenic strains. Mouse Genome 92, 666.Google Scholar
Lo, C. (1983). Transformation by iontophoretic microinjection of DNA: multiple integrations without tandem insertions. Molecular and Cellular Biology 3, 1803–1814.Google ScholarPubMed
Lo, C. (1986). Localization of low abundance DNA sequences in tissue sections by in situ hybridization. Journal of Cell Science 81, 143–162.CrossRefGoogle ScholarPubMed
Lo, C. W., Coulling, M. & Kirby, C. (1987). Tracking of mouse cell lineage using microinjected DNA sequences: analyses using genomic Southern blotting and tissue-section in situ hybridizations. Differentiation 35, 37–44.CrossRefGoogle ScholarPubMed
Lo, C. W., Diaz, R. & Kirby, C. (1992). Iontophoretic DNA injections and the production of transgenic mice. Mouse Genome 90, 684–686.Google Scholar
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, 185–195.CrossRefGoogle ScholarPubMed
Nagy, A., Sass, M. & Markkula, M. (1989). Systematic non-uniform distribution of parthenogenetic cells in adult mouse chimaeras. Development 106, 321–324.CrossRefGoogle ScholarPubMed
Oster-Granite, M. L. & Gearhart, J. (1981). Cell lineage analysis of cerebellar Purkinje cells in mouse chimaeras. Developmental Biology 85, 199–208.CrossRefGoogle Scholar
Palmer, S. J., & Burgoyne, P. S., (1991). In situ analysis of fetal, prepubertal and adult XX ↔ XY testes: Sertoli cells are predominantly, but not exclusively, XY. Development 112, 265–268.CrossRefGoogle Scholar
Thomson, J. A., & Solter, D., (1988 a). Transgenic markers for mammalian chimeras. Roux's Archives of Developmental Biology 197, 63–65.CrossRefGoogle ScholarPubMed
Thomson, J. A., & Solter, D., (1988 b). The developmental fate of androgenetic, parthenogenetic and gynogenetic cells in chimeric gastrulating mouse embryos. Genes and Development 2, 1344–1351.CrossRefGoogle ScholarPubMed
Thomson, J. A., & Solter, D., (1989). Chimeras between parthenogenetic or androgenetic blastomeres and normal embryos: allocation to the inner cell mass and trophectoderm. Developmental Biology 131, 580–583.CrossRefGoogle ScholarPubMed
West, J. D., (1984). Cell markers. In Chimaeras in Developmental Biology (ed. Douarinand, N. L. and McLaren, A.). pp. 39–63. London: Academic Press.Google Scholar
West, J. D., Bücher, Th., Linke, I. M., & Dünnwald, M., (1984). Investigation of variability among mouse aggregation chimaeras and X chromosome inactivation mosaics. Journal of Embryology and Experimental Morphology 84, 309–329.Google ScholarPubMed
West, J. D., Everett, C. A., & Keighren, M., (1995 a). Corrections to transgenic nomenclature. Mouse Genome 93, 145.Google Scholar
West, J. D., & Flockhart, J. H., (1994). Genotypically unbalanced diploid ↔ diploid foetal mouse chimaeras: possible relevance to human confined mosaicism. Genetical Research 63, 87–99.CrossRefGoogle ScholarPubMed
West, J. D., Flockhart, J. H., & Keighren, M., (1995 b). Biochemical evidence for cell fusion in placentas of mouse aggregation chimeras. Developmental Biology 168, 76–85.CrossRefGoogle ScholarPubMed
West, J. D., Flockhart, J. H., & Kissenpfennig, A., (1995 c). A maternal effect on the composition of mouse aggregation chimaeras. Genetical Research 65, 29–40.CrossRefGoogle ScholarPubMed