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Relative transgene expression frequencies in homozygous versus hemizygous transgenic mice

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Abstract

We have used a simple binomial model of stochastic transgene inactivation at the level of the chromosome or transgene, rather than the cellular level, for the analysis of two mouse transgenic lines that show variegated patterns of expression. This predicts the percentages of cells that express one, both or neither alleles of the transgene in homozygotes from the observed percentages of cells, which express the transgene in hemizygotes. It adequately explained the relationship between the numbers of cells expressing the transgene in hemizygous and homozygous mosaic 21OH/LacZ mouse adrenals and mosaic BLG/7 mouse mammary glands. The binomial model also predicted that a small proportion of cells in mosaic mammary glands of BLG/7 homozygotes would express both BLG/7 alleles but published data indicated that all cells expressing the transgene showed monoallelic expression. Although it didn’t fit all of the BLG/7 data as precisely as a more complex model, which used several ad hoc assumptions to explain these results, the simple binomial model was able to explain the relationship in observed transgene expression frequencies between hemizygous and homozygous mosaic tissues for both 21OH/LacZ and BLG/7 mice. It may prove to be a useful general model for analysing other transgenic animals showing mosaic transgene expression.

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Acknowledgments

We thank the staff at BRR, University of Edinburgh for expert animal husbandry and specialised technical services and Ronnie Grant for help with the illustrations. We are grateful to Springer Science+Business Media B.V. for permission to reproduce Fig. 3e, f. This work was supported, in part, by a Tenovus Scotland grant award (E04/6) to JDW and SDM; and BBSRC support to both MLO and CBAW. S-PC is grateful for an award from the University of Edinburgh Common Bursaries Fund.

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  1. Su-Ping Chang

    Present address: Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, 3002, Australia

Authors and Affiliations

  1. Genes and Development Group, Centre for Integrative Physiology, School of Clinical Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK

    Su-Ping Chang & John D. West

  2. Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9PS, UK

    Margaret L. Opsahl & C. Bruce A. Whitelaw

  3. Clinical Biochemistry Section, Division of Health Sciences, University of Edinburgh Medical School, Chancellor’s Building, 49 Little France Crescent, Edinburgh, EH16 1SB, UK

    Steven D. Morley

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  1. Su-Ping Chang
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  2. Margaret L. Opsahl
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  3. C. Bruce A. Whitelaw
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  4. Steven D. Morley
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  5. John D. West
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Correspondence to John D. West.

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Chang, SP., Opsahl, M.L., Whitelaw, C.B.A. et al. Relative transgene expression frequencies in homozygous versus hemizygous transgenic mice. Transgenic Res 22, 1143–1154 (2013). https://doi.org/10.1007/s11248-013-9732-5

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  • DOI: https://doi.org/10.1007/s11248-013-9732-5

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