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Proinsulin expression by Hassall's corpuscles in the mouse thymus



Proinsulin expression by Hassall's corpuscles in the mouse thymus



Diabetes 53(2): 354-359



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.

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Accession: 012456893

Download citation: RISBibTeXText

PMID: 14747285

DOI: 10.2337/diabetes.53.2.354


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