Crispr-Cas9 mediated complete deletion of glucagon receptor in mice display hyperglucagonemia and a-cell hyperplasia

Glucagon receptor plays an important role in the regulation of glucose metabolism. Studies have revealed that glucagon receptor antagonism is a potential effective treatment for diabetes. However, the functions of GCGR have not been fully illustrated. Although two Gcgr truncation knockout mice models have been widely used for GCGR function studies, truncated gene may remain neomorphic and/or dominant -negative function. In this study, we took the advantages of Crispr-Cas9 technique and generated a novel allele of GCGR in the mouse that yields complete loss of GCGR protein. Our studies reveal that complete deletion of Gcgr results in hyperglucagonemia, a-cell hyperplasia, improvement of glucose tolerance. These results are similar to the Gcgr-truncated mutation in mice. Hence, we provide a novel strain of GCGR knockout mice for the GCGR function studies.

Automated summary

Glucagon receptor antagonism is a potential effective treatment for diabetes, but its functions have not been fully elucidated. Using Crispr-Cas9 technique, researchers generated a novel allele of GCGR in mice that completely lacks GCGR protein. Complete deletion of Gcgr leads to hyperglucagonemia, α-cell hyperplasia, and improvement of glucose tolerance, similar to Gcgr-truncated mutation in mice. This novel GCGR knockout mouse strain provides a valuable tool for studying GCGR function.