Identification and functional analysis of CBLB mutations in type 1 diabetes
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- 作者：Norihide Yokoi ; Yuuka Fujiwara ; He-Yao Wang ; Mai Kitao ; Chihiro Hayashi ; Tomohiro Someya ; Masao Kanamori ; Yutaka Oiso ; Naoko Tajima ; Yuichiro Yamada ; Yutaka Seino ; Hiroshi Ikegami ; Susumu Seino
- 关键词：Autoimmunity ; CBLB ; Genetics ; Mutation ; Susceptibility ; T-cell ; Type 1 diabetes
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2008
- 出版时间：28 March 2008
- 年：2008
- 卷：368
- 期：1
- 页码：37-42
- 全文大小：132 K
文摘
Casitas B-lineage lymphoma b (Cblb) is a negative regulator of T-cell activation and dysfunction of Cblb in rats and mice results in autoimmunity. In particular, a nonsense mutation in Cblb has been identified in a rat model of autoimmune type 1 diabetes. To clarify the possible involvement of CBLB mutation in type 1 diabetes in humans, we performed mutation screening of CBLB and characterized functional properties of the mutations in Japanese subjects. Six missense mutations (A155V, F328L, N466D, K837R, T882A, and R968L) were identified in one diabetic subject each, excepting N466D. Of these mutations, F328L showed impaired suppression of T-cell activation and was a loss-of-function mutation. These data suggest that the F328L mutation is involved in the development of autoimmune diseases including type 1 diabetes, and also provide insight into the structure–function relationship of CBLB protein.