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Proinsulin Expression by Hassall’s Corpuscles in the Mouse Thymus

2004; American Diabetes Association; Volume: 53; Issue: 2 Linguagem: Inglês

10.2337/diabetes.53.2.354

1939-327X

Aziz Alami Chentoufi, Michael Palumbo, Constantin Polychronakos,

Diabetes Management and Research

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 β-galactosidase (β-Gal) under the control of an endogenous insulin promoter, we found that thymic proinsulin and β-Gal transcripts were detectable at high levels in purified thymic epithelial cells. Immunohistochemical analysis of β-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 β-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.