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A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
PPARdelta status and mismatch repair mediated neoplasia in the mouse intestine
Karen R Reed1, Owen J Sansom, Anthony J Hayes
1Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF103US, UK. reedkr@cf.ac.uk
Background:
Therapeutic regulation of PPARdelta activity using selective agonists has been proposed for various disorders. However, the consequences of altered peroxisome proliferator-activated receptor delta (PPARdelta) activity in the context of intestinal tumourigenesis remain somewhat unclear. Contradictory evidence suggesting PPARdelta either attenuates or potentiates intestinal neoplasia. To further investigate the PPARdelta dependency of intestinal tumourigenesis, we have analysed the consequences of PPARdelta deficiency upon intestinal neoplasia occurring in mice with impaired mismatch DNA repair.
Methods:
Mice deficient for both PPARdelta and the mismatch repair gene Mlh1 were produced and the incidence and severity of intestinal neoplasia recorded.
Results:
No significant differences between the control genotypes and the double mutant genotypes were recorded indicating that deficiency of PPARdelta does not modify impaired mismatch repair induced neoplasia.
Conclusion:
In contrast with the previously observed acceleration of intestinal neoplasia in the context of the ApcMin/+ mouse, PPARdelta deficiency does not alter the phenotype of mismatch repair deficiency. This data supports the notion that PPARdelta is not required for adenoma formation and indicate that any pro-tumourigenic effect of PPARdelta inactivation may be highly context dependent.
Insights
Peroxisome proliferator-activated receptor delta (PPARdelta) deficiency does not affect intestinal tumor development in mice with faulty DNA repair. This suggests PPARdelta
Area of Science:
- Gastroenterology
- Oncology
- Molecular Biology
Background:
- Peroxisome proliferator-activated receptor delta (PPARdelta) modulation is explored for various diseases.
- The role of PPARdelta in intestinal cancer is debated, with conflicting evidence on its effects.
- Investigating PPARdelta's role in intestinal tumorigenesis is crucial for understanding cancer development.
Purpose of the Study:
- To determine the effect of PPARdelta deficiency on intestinal neoplasia in mice with impaired DNA mismatch repair.
- To clarify the context-dependent role of PPARdelta in intestinal tumor formation.
Main Methods:
- Generated mice lacking both PPARdelta and the Mlh1 mismatch repair gene.
- Assessed the incidence and severity of intestinal neoplasia in these mice.
Main Results:
- No significant differences in intestinal neoplasia were observed between mice with and without PPARdelta deficiency when DNA mismatch repair was impaired.
- PPARdelta deficiency did not alter the tumor phenotype associated with mismatch repair deficiency.
Conclusions:
- PPARdelta deficiency does not influence the development of intestinal tumors in the context of impaired mismatch repair.
- This study indicates that PPARdelta is not essential for adenoma formation and its pro-tumorigenic effects are context-specific.
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