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Diabetes 53:354-359, 2004
© 2004 by the American Diabetes Association, Inc.

Proinsulin Expression by Hassall’s Corpuscles in the Mouse Thymus

Aziz Alami Chentoufi, Michael Palumbo, and Constantin Polychronakos

Endocrine Genetics Laboratory, McGill University Health Center (Montreal Children’s Hospital-Research Institute), Montreal, Quebec, Canada

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

Address correspondence and reprint requests to Constantin Polychronakos, Endocrine Genetics Laboratory, McGill University Health Center (Montreal Children’s Hospital) Research Institute, 2300 Tupper, Office C244, Montreal, PQ, Canada H3H 1P3. E-mail: constantin polychronakos{at}mcgill.ca


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Copyright © 2004 by the American Diabetes Association.