-
- Il-mi Okazaki
- 1Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
-
- Hiroshi Hiai
- 2Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
-
- Naoki Kakazu
- 3Department of Hygiene, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
-
- Shuichi Yamada
- 4Department of Cell Biology, Institute for Virus Research, Kyoto University, 53 Kawaracho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
-
- Masamichi Muramatsu
- 1Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
-
- Kazuo Kinoshita
- 1Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
-
- Tasuku Honjo
- 1Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
書誌事項
- 公開日
- 2003-05-05
- DOI
-
- 10.1084/jem.20030275
- 公開者
- Rockefeller University Press
この論文をさがす
説明
<jats:p>Genome stability is regulated by the balance between efficiencies of the repair machinery and genetic alterations such as mutations and chromosomal rearrangements. It has been postulated that deregulation of class switch recombination (CSR) and somatic hypermutation (SHM), which modify the immunoglobulin (Ig) genes in activated B cells, may be responsible for aberrant chromosomal translocations and mutations of non-Ig genes that lead to lymphocyte malignancy. However, the molecular basis for these genetic instabilities is not clearly understood. Activation-induced cytidine deaminase (AID) is shown to be essential and sufficient to induce both CSR and SHM in artificial substrates in fibroblasts as well as B cells. Here we show that constitutive and ubiquitous expression of AID in transgenic mice caused both T cell lymphomas and dysgenetic lesions of epithelium of respiratory bronchioles (micro-adenomas) in all individual mice. Point mutations, but not translocations, were massively introduced in expressed T cell receptor (TCR) and c-myc genes in T lymphoma cells. The results indicate that AID can mutate non-Ig genes including oncogenes, implying that aberrant AID expression could be a cause of human malignancy.</jats:p>
収録刊行物
-
- The Journal of Experimental Medicine
-
The Journal of Experimental Medicine 197 (9), 1173-1181, 2003-05-05
Rockefeller University Press
