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Updated: Jun 4, 2026
Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
Published on: April 13, 2015
Regeneration of the exocrine pancreas is delayed in telomere-dysfunctional mice
Guido von Figura1, Martin Wagner, Kodandaramireddy Nalapareddy
1Institute of Molecular Medicine and Max-Planck-Research-Group on Stem Cell Aging, University of Ulm, Ulm, Germany.
Introduction:
Telomere shortening is a cell-intrinsic mechanism that limits cell proliferation by induction of DNA damage responses resulting either in apoptosis or cellular senescence. Shortening of telomeres has been shown to occur during human aging and in chronic diseases that accelerate cell turnover, such as chronic hepatitis. Telomere shortening can limit organ homeostasis and regeneration in response to injury. Whether the same holds true for pancreas regeneration in response to injury is not known.
Methods:
In the present study, pancreatic regeneration after acute cerulein-induced pancreatitis was studied in late generation telomerase knockout mice with short telomeres compared to telomerase wild-type mice with long telomeres.
Results:
Late generation telomerase knockout mice exhibited impaired exocrine pancreatic regeneration after acute pancreatitis as seen by persistence of metaplastic acinar cells and markedly reduced proliferation. The expression levels of p53 and p21 were not significantly increased in regenerating pancreas of late generation telomerase knockout mice compared to wild-type mice.
Conclusion:
Our results indicate that pancreatic regeneration is limited in the context of telomere dysfunction without evidence for p53 checkpoint activation.
Insights
Telomere shortening limits pancreas regeneration in mice with short telomeres. This impaired regeneration occurs without activating the p53 checkpoint, suggesting telomere dysfunction restricts pancreatic repair.
Area of Science:
- Cellular Biology
- Gastroenterology
- Aging Research
Background:
- Telomere shortening, a natural process limiting cell division, is linked to aging and chronic diseases.
- This mechanism can impair organ repair and regeneration.
- Its role in pancreatic regeneration remains unclear.
Purpose of the Study:
- To investigate the impact of telomere dysfunction on pancreatic regeneration.
- To compare regeneration in mice with short telomeres versus those with long telomeres.
Main Methods:
- Studied pancreatic regeneration in telomerase knockout mice (short telomeres) and wild-type mice (long telomeres) after pancreatitis.
- Induced acute pancreatitis using cerulein.
Main Results:
- Telomerase knockout mice showed significantly impaired pancreatic regeneration.
- These mice exhibited persistent metaplasia and reduced cell proliferation in the exocrine pancreas.
- No significant increase in p53 or p21 expression was observed in regenerating pancreata of knockout mice.
Conclusions:
- Telomere dysfunction impairs pancreatic regeneration.
- This impairment occurs independently of p53 checkpoint activation.
- Findings highlight telomere length as a critical factor in pancreatic repair capacity.
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