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

Sansom, Owen J. ORCID: https://orcid.org/0000-0001-9540-3010, Bishop, Stefan Mark, Bird, Adrian and Clarke, Alan Richard ORCID: https://orcid.org/0000-0002-4281-426X 2004. MBD4 deficiency does not increase mutation or accelerate tumorigenesis in mice lacking MMR. Oncogene 23 (33) , pp. 5693-5696. 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 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Uncontrolled Keywords:	MBD4; MMR; DNA methylation; cancer.
Publisher:	Nature Publishing
ISSN:	0950-9232
Last Modified:	25 Oct 2022 10:11
URI:	https://orca.cardiff.ac.uk/id/eprint/61361

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