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

Farnaz Shamsi, Rosanna Parlato, Patrick Collombat, Ahmed Mansouri

Research output: Contribution to journalArticlepeer-review


The putative induction of adult b-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 b-cell ablation mouse model, in which the b-cell mass progressively declines, as seen in type 1 diabetes. The model is based on the b-cell specific genetic ablation of the transcription initiation factor 1A, TIF-IA, essential for RNA Polymerase I activity (TIF-IAD/D). Using this approach, we induced a slow apoptotic response that eventually leads to a protracted b-cell death. In this model, we observed b-cell regeneration that resulted in a complete recovery of the b-cell mass and normoglycemia. In addition, we showed that adaptive proliferation of remaining b-cells is the prominent mechanism acting to compensate for the massive b-cell loss in young but also aged mice. Interestingly, at any age, we also detected b-like cells expressing the glucagon hormone, suggesting a transition between a- and b-cell identities or vice versa. Taken together, the TIF-IAD/D mouse model can be used to investigate the potential therapeutic approaches for type 1 diabetes targeting b-cell regeneration.

Original languageEnglish (US)
Pages (from-to)3948-3957
Number of pages10
JournalCell Cycle
Issue number24
StatePublished - Dec 15 2014


  • B-cell proliferation
  • Diabetes
  • Insulin
  • Islet of langerhans
  • Pancreatic b-cell
  • Regeneration
  • TIF-IA

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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