Injection of exogenous insulin to treat permanent neonatal diabetic model dogs, homozygous mutants on the left, chimeric mutants on the right
Injection of exogenous insulin to treat permanent neonatal diabetic model dogs, homozygous mutants on the left, chimeric mutants on the right
Diabetes is the third most common disease after cardiovascular diseases and tumors
GCK GCK gene mutations account for a large proportion of juvenile diabetes, and most of them are single-nucleotide mutations.
GCK For the first time, researchers tried to use a single-base editor to make point mutations in the canine GCK gene, so that the CAG codon on the GCK gene was converted from C to T, thereby introducing a stop codon, terminating the translation of GCK early , and completely losing the GCK protein.
GCK GCK CAG GCK GCK In this experiment, a total of 56 fertilized eggs were transplanted, 17 puppies were laid, and 4 GCK gene-edited dogs were obtained , of which 3 were homozygous mutations and 1 was chimera
GCK GCK Researchers conducted GO enrichment analysis on RNA sequencing results and found that permanent neonatal diabetes model dogs injected with exogenous insulin can promote metabolism of lipids and fatty acids, and maintain a relatively normal level of physiological indicators in dogs, thereby enabling Its survival time is prolonged, and these characteristics are consistent with the symptoms of permanent neonatal diabetes in humans
The single-base gene-edited dog will provide an ideal animal model for studying the mechanism of human neonatal diabetes and developing new treatment methods, such as drug therapy, stem cell therapy and gene therapy
"Obtaining an animal model that can accurately simulate the disease in humans is of great significance to the research on the occurrence mechanism of the disease and the development of new treatment methods
Related research work has been funded by the National Key R&D Program, the Strategic Pilot Program of the Chinese Academy of Sciences, and the Guangdong Province and Guangzhou Municipal Science and Technology Programs
Related paper information: https://doi.
https://doi.
org/10.
1038/s41421-021-00304-y
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