Generation of LEPR K nockout Rabbits with CRISPR/CAS9 System

This is the authors' abstract. We don't add key points for this paper.

In humans mutations in the LEPR gene, encoding leptin hormone receptor, are associated with the development of morbid obesity, lipid metabolism dysregulation, defects of fertility. In rodents spontaneous mutations in Lepr gene have been described. Lepr knock-out (KO) animals have been generated using classical KO technology or CRISPR/Cas9 system. In rodents lipid metabolism is significantly different from that in humans or rabbits, therefore rabbits are considered as the most relevant model of morbid obesity and lipid metabolism dysregulation in humans, but so far LEPR knock-out rabbits have not been reported. Here using CRISPR/Cas9 system we generated LEPR knock-out rabbit by introducing a deletion of the region around exon 10 of the LEPR gene. We showed that the body weight of the knock-out rabbit was significantly higher than an average body weight of the wild type rabbits. CRISPR/Cas9-mediated technology for the generation of the LEPR knock-out rabbits will allow for the development of the model of morbid obesity and endocrine defects in humans due to leptin receptor mutations.