Phenotypic Characterization and Comparison of Cystic Fibrosis Rat Models Generated Using CRISPR/Cas9 Gene Editing

Area of Science:

• Biomedical Research
• Genetics
• Animal Models

Background:

• Cystic Fibrosis (CF) research requires robust animal models to understand disease progression and test new treatments.
• Current models may not fully recapitulate the complexity of human CF.

Purpose of the Study:

• To develop and characterize novel rat models of cystic fibrosis using advanced gene editing techniques.
• To provide reliable preclinical tools for CF pathophysiology and therapeutic studies.

Main Methods:

• Utilized CRISPR/Cas9 gene editing to create two distinct CF rat models: one with the common human Phe508del mutation and a CFTR knockout.
• Conducted comprehensive phenotypic characterization including nasal potential difference, gene expression analysis (qRT-PCR, RNAscope), protein localization (immunohistochemistry), and histopathology.

Main Results:

• Both CF rat models displayed hallmark CF manifestations such as reduced survival and intestinal obstruction.
• Observed significant bioelectric defects in nasal epithelium and characteristic histopathologic changes in the trachea, large intestine, and pancreas.
• Identified abnormalities in male reproductive tract development in the generated CF rat models.

Conclusions:

• The developed CF rat models accurately mimic critical aspects of human cystic fibrosis.
• These models offer valuable platforms for longitudinal studies of CF disease mechanisms and the evaluation of novel therapeutic interventions.