Proinsulin expression by Hassall's corpuscles in the mouse thymus.
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.
Chentoufi
Aziz Alami
AA
Endocrine Genetics Laboratory, McGill University Health Center (Montreal Children's Hospital-Research Institute), Montreal, Quebec, Canada.
Palumbo
Michael
M
Polychronakos
Constantin
C
D000818:Animals; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology; D051379:Mice; D011384:Proinsulin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*
D018076:DNA, Complementary; D011384:Proinsulin