| First Author | Nilsen H | Year | 2003 |
| Journal | Oncogene | Volume | 22 |
| Issue | 35 | Pages | 5381-6 |
| PubMed ID | 12934097 | Mgi Jnum | J:85353 |
| Mgi Id | MGI:2674176 | Doi | 10.1038/sj.onc.1206860 |
| Citation | Nilsen H, et al. (2003) Gene-targeted mice lacking the Ung uracil-DNA glycosylase develop B-cell lymphomas. Oncogene 22(35):5381-6 |
| abstractText | Mice deficient in the Ung uracil-DNA glycosylase have an increased level of uracil in their genome, consistent with a major role of Ung counteracting U:A base pairs arising by misincorporation of dUMP during DNA replication. A complementary uracil-excising activity apparently acts on premutagenic U:G lesions resulting from deamination of cytosine throughout the genome. However, Ung specifically processes U:G lesions targeted to immunoglobulin variable (V) genes during somatic hypermutation and class-switch recombination. Gene-targeted Ung(-/-) null mice remained tumour-free and showed no overt pathological phenotype up to approximately 12 months of age. We have monitored a large cohort of ageing Ung(-/-) mice and, beyond 18 months of age, they had a higher morbidity than Ung(+/+) controls. Post-mortem analyses revealed pathological changes in lymphoid organs, abnormal lymphoproliferation, and a greatly increased incidence of B-cell lymphomas in older Ung-deficient mice. These are the first data reporting the development of spontaneous malignancies in mice due to deficiency in a DNA glycosylase. Furthermore, they support a specific role for Ung in the immune system, with lymphomagenesis being related to perturbed processing of antibody genes in germinal centre B cells. |
