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

Sansom, O. , Bishop, S., Bird, A. and Clarke, A. (2004) MBD4 deficiency does not increase mutation or accelerate tumorigenesis in mice lacking MMR. Oncogene, 23(33), pp. 5693-5696. (doi:10.1038/sj.onc.1207767)

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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 DIb-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

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sansom, Professor Owen
Authors: Sansom, O., Bishop, S., Bird, A., and Clarke, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncogene
ISSN:0950-9232

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