Generation of LEPR Knockout Rabbits with CRISPR/CAS9 System

Area of Science:

• Genetics and Genomics
• Metabolic Disorders
• Animal Models

Background:

• The leptin receptor (LEPR) gene is crucial for regulating body weight and metabolism.
• Mutations in LEPR are linked to morbid obesity and metabolic dysfunction in humans.
• Rabbits are a relevant model for human obesity due to metabolic similarities.

Purpose of the Study:

• To generate a LEPR knockout rabbit model using CRISPR/Cas9.
• To establish a relevant animal model for studying human obesity and leptin receptor mutations.
• To investigate the role of LEPR in metabolic regulation in rabbits.

Main Methods:

• CRISPR/Cas9 gene editing was employed to create a deletion in the LEPR gene, specifically targeting exon 10.
• The generated LEPR knockout rabbit was characterized and compared to wild-type rabbits.
• Phenotypic analysis focused on body weight and indicators of metabolic dysregulation.

Main Results:

• A LEPR knockout rabbit was successfully generated via CRISPR/Cas9-mediated gene editing.
• The LEPR knockout rabbit demonstrated significantly higher body weight compared to wild-type controls.
• This confirms the role of LEPR in weight regulation in rabbits.

Conclusions:

• CRISPR/Cas9-mediated generation of LEPR knockout rabbits provides a novel animal model.
• This model is suitable for studying morbid obesity and endocrine defects associated with leptin receptor mutations.
• The LEPR knockout rabbit advances research into human metabolic diseases.