Proinsulin Expression by Hassall’s Corpuscles in the Mouse Thymus
- Endocrine Genetics Laboratory, McGill University Health Center (Montreal Children’s Hospital-Research Institute), Montreal, Quebec, Canada
- 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
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.
- β-Gal, β-galactosidase
- DC, dendritic cell
- mTEC, medullary epithelial cell
- HC, Hassall’s corpuscle
- TEC, thymic epithelial cell
Footnotes
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A.A.C. and M.P. contributed equally to this work.
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- Accepted October 22, 2003.
- Received July 4, 2003.
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