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  A genetic mouse model for progressive ablation and regeneration of insulin producing beta-cells.

Shamsi, F., Parlato, R., Collombat, P., & Mansouri, A. (2015). A genetic mouse model for progressive ablation and regeneration of insulin producing beta-cells. Cell Cycle, 13(24), 3948-3957. doi:10.4161/15384101.2014.952176.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-6BC0-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-6D2C-9
Genre: Journal Article

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 Creators:
Shamsi, F.1, Author              
Parlato, R., Author
Collombat, P., Author
Mansouri, A.1, Author              
Affiliations:
1Research Group of Molecular Cell Differentiation, MPI for Biophysical Chemistry, Max Planck Society, ou_578588              

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Free keywords: Beta-cell proliferation; diabetes; insulin; islet of Langerhans; pancreatic beta-cell; regeneration; TIF-IA
 Abstract: The putative induction of adult -cell regeneration represents a promising approach for the treatment of type 1 diabetes. Toward this ultimate goal, it is essential to develop an inducible model mimicking the long-lasting disease progression. In the current study, we have established a novel -cell ablation mouse model, in which the -cell mass progressively declines, as seen in type 1 diabetes. The model is based on the -cell specific genetic ablation of the transcription initiation factor 1A, TIF-IA, essential for RNA Polymerase I activity (TIF-IA(/)). Using this approach, we induced a slow apoptotic response that eventually leads to a protracted -cell death. In this model, we observed -cell regeneration that resulted in a complete recovery of the -cell mass and normoglycemia. In addition, we showed that adaptive proliferation of remaining -cells is the prominent mechanism acting to compensate for the massive -cell loss in young but also aged mice. Interestingly, at any age, we also detected -like cells expressing the glucagon hormone, suggesting a transition between - and -cell identities or vice versa. Taken together, the TIF-IA(/) mouse model can be used to investigate the potential therapeutic approaches for type 1 diabetes targeting -cell regeneration.

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Language(s): eng - English
 Dates: 2015-01-03
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.4161/15384101.2014.952176
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Title: Cell Cycle
Source Genre: Journal
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Pages: - Volume / Issue: 13 (24) Sequence Number: - Start / End Page: 3948 - 3957 Identifier: -