Proinsulin Expression by Hassall's Corpuscles in the Mouse Thymus

Abstract

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.