The Missing Link: Cre Pigs for Cancer Research

Area of Science:

• Genetics and Genomics
• Comparative Oncology
• Transgenic Animal Models

Background:

• The Cre/loxP system is vital for generating genetically engineered animal models with spatiotemporal control of gene expression, particularly for cancer research.
• While mouse models are foundational, large animal models like pigs offer complementary translational research opportunities.
• Existing large animal models lack specific Cre-driver lines for major human cancers, hindering translational studies.

Purpose of the Study:

• To develop novel porcine Cre-driver lines for modeling human pancreatic cancer.
• To establish a method for generating tissue- and cell-type-specific Cre expression in pigs.
• To provide a missing resource for large animal models in human cancer research.

Main Methods:

• CRISPR/Cas9 gene editing was employed to insert codon-improved Cre (iCre) into the porcine PTF1A gene.
• Dual fluorescent reporter pigs were utilized to validate the tissue- and cell-type-specific function of the generated Cre-driver lines.
• The methodology is adaptable for creating other porcine Cre-driver lines.

Main Results:

• Successfully generated porcine Cre-driver lines targeting the PTF1A gene, crucial for pancreatic development.
• Demonstrated tissue- and cell-type-specific Cre activity in the generated pig models using fluorescent reporters.
• Validated the utility of the generated Cre-driver lines for potential pancreatic cancer modeling in pigs.

Conclusions:

• The developed CRISPR/Cas9-based method enables efficient generation of porcine Cre-driver lines for specific gene targeting.
• These novel pig models provide a valuable resource for studying human pancreatic cancer in a large animal setting.
• The adaptable methodology facilitates the creation of diverse Cre-driver lines, advancing large animal models for various human diseases.