Proinsulin expression by Hassall's corpuscles in the mouse thymus
Proinsulin expression by Hassall's corpuscles in the mouse thymus
复制标题
DOI：
10.2337/diabetes.53.2.354
复制
发表时间：
2004-02-01
期刊：
影响因子：
7.7
通讯作者：
Polychronakos, C
中科院分区：
文献类型：
--
作者：
Chentoufi, AA;Palumbo, M;Polychronakos, C
胸腺表达胰岛素原，在许多其他组织特异性抗原中，遗传决定的胸腺胰岛素原低表达与胰岛素原特异性自身反应性T细胞耐受性受损和1型糖尿病易感性有关。胸腺中胰岛素原表达的细胞和分子生物学尚不清楚，关于胰岛素原产生细胞的身份也存在相互矛盾的报道。利用在内源性胰岛素启动子控制下表达β-半乳糖苷酶(β-Gal)的转基因小鼠，我们发现在纯化的胸腺上皮细胞中可以检测到高水平的胸腺胰岛素原和β-Gal转录本。对β-半乳糖活性的免疫组织化学分析表明，大多数胰岛素原的表达可以由罕见的哈撒尔小体的髓质上皮细胞来解释。此外，对β-Gal阳性细胞的流式细胞术分析表明，只有1-3%的上皮细胞表达胰岛素原，这一技术将为我们提供一种分离小鼠胸腺中胰岛素原产生细胞的方法。
The thymus expresses proinsulin, among many other tissue-specific antigens, and the inheritance of genetically determined low thymic proinsulin expression has been associated with impaired proinsulin-specific autoreactive T-cell tolerance and type 1 diabetes susceptibility. The cellular and molecular biology of proinsulin expression in the thymus remains unknown, and contradictory reports exist regarding the identity of proinsulin-producing cells. Using knock-in mice expressing beta-galactosidase (beta-Gal) under the control of an endogenous insulin promoter, we found that thymic proinsulin and beta-Gal transcripts were detectable at high levels in purified thymic epithelial cells. Immunohistochemical analysis of beta-Gal activity showed that most proinsulin expression can be accounted for by rare medullary epithelial cells of the Hassall's corpuscles. Moreover, flow cytometry analyses of beta-Gal-positive cells showed that only 1-3% of all epithelial cells express proinsulin, and this technique will now provide us with a method for isolating the proinsulin-producing cells in mouse thymus.