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MBD4 deficiency does not increase mutation or accelerate tumorigenesis in mice lacking MMR

Oncogene volume 23, pages 5693–5696 (2004)Cite this article

Abstract

Mbd4 (methyl-binding domain 4) has been shown to be mutated in a high percentage of mismatch repair (MMR)-deficient colorectal tumours that exhibit microsatellite instability (MSI). However, the significance of these mutations is still unclear as they are predominantly monoallelic and the majority occur at a poly-A tract. Apart from MMR-deficient tumours, no other reports of mutations of Mbd4 in human neoplasia are as yet published. To address the significance of loss of Mbd4 in the absence of MMR, we have crossed Mbd4-deficient mice to mice lacking DNA MMR. We show that, in the context of MMR deficiency, additional loss of Mbd4 does not alter spontaneous mutation frequency at the endogenous Dlb-1b locus, nor does it modify tumour onset, tumour spectrum or MSI compared to singly mutant Msh2 or Mlh1 mice. Taken together, these findings show that nullizygosity or heterozygosity for Mbd4 does not affect MMR-dependent tumorigenesis.

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Acknowledgements

This work was supported by CR-UK, The Wales Gene Park and the Wellcome Trust. We thank Michael Liskay for supply of the Mlh1-deficient mice and Nathan Hill for maintenance of animal stocks.

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Authors and Affiliations

  1. School of Biosciences, University of Cardiff, PO Box 911, Museum Avenue, Cardiff, CF10 3US, UK

    Owen J Sansom, Stefan M Bishop & Alan R Clarke

  2. The Wellcome Trust Centre for Cell Biology, ICMB, University of Edinburgh, Edinburgh, EH9 3JR, UK

    Adrian Bird

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  1. Owen J Sansom
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Correspondence to Alan R Clarke.

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Sansom, O., Bishop, S., Bird, A. et al. MBD4 deficiency does not increase mutation or accelerate tumorigenesis in mice lacking MMR. Oncogene 23, 5693–5696 (2004). https://doi.org/10.1038/sj.onc.1207767

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