Identification and functional analysis of CBLB mutations in type 1 diabetes
Identification and functional analysis of CBLB mutations in type 1 diabetes
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DOI：
10.1016/j.bbrc.2008.01.032
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发表时间：
2008-03-28
影响因子：
3.1
通讯作者：
Seino, Susumu
中科院分区：
文献类型：
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作者：
Yokoi, Norihide;Fujiwara, Yuuka;Seino, Susumu
Casitas B 系淋巴瘤 b (Cblb) 是 T 细胞激活的负调节因子，在大鼠和小鼠中 Cblb 功能障碍会导致自身免疫。特别是，在自身免疫性 I 型糖尿病大鼠模型中发现了 Cblb 的无义突变。为了阐明 CBLB 突变可能与人类 I 型糖尿病有关，我们对日本受试者进行了 CBLB 突变筛查并表征了突变的功能特性。除 N466D 外，在一名糖尿病受试者中分别鉴定出 6 种错义突变（A155V、F328L、N466D、K837R、T882A 和 R968L）。在这些突变中，F328L 显示出对 T 细胞激活的抑制受损，并且是一种功能丧失突变。这些数据表明F328L突变参与包括I型糖尿病在内的自身免疫性疾病的发生，也为了解CBLB蛋白的结构与功能关系提供了见解。 (C) 2008 Elsevier Inc. 保留所有权利。
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 I diabetes. To clarify the possible involvement of CBLB mutation in type I 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 I diabetes, and also provide insight into the structure-function relationship of CBLB protein. (C) 2008 Elsevier Inc. All rights reserved.