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Recently, the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences cooperated with Beijing Sino Valley Biotechnology Co.
, Ltd.
to use a single-base editor to perform point mutations on glucokinase, successfully cultivating the world’s first human permanent neonatal diabetic canine model.
Related papers " Generation of Permanent Neonatal Diabetes mellitus Dogs with glucokinase Point mutations Base editin through G" published online in Cell Discovery magazine
.
Diabetes is the third most common disease after cardiovascular diseases and tumors
.
At present, there are more than 400 million diabetic patients in the world, and more than 100 million diabetic patients in China
Obtaining an animal model that can accurately simulate the human disease is of great significance to the research on the occurrence mechanism of the disease and the development of new treatment methods
.
Dogs are an omnivorous animal, very close to humans in terms of metabolism, physiology, living habits and anatomical characteristics, so it is an ideal animal model for the study of human diabetes
This research is the first attempt to use a single-base editor to perform point mutations in the canine GCK gene, so that the CAG codon on the GCK gene completes the C to T transition, thereby introducing a stop codon, terminating the translation of GCK early, and completely losing the GCK protein.
Active
.
The process is to first obtain the fertilized eggs from the donor dog, and inject the in vitro transcribed base editor mRNA and sgRNA into the fertilized eggs with the help of a microscope operating system, and then transplant the injected fertilized eggs into the oviduct of the surrogate dog to make It continues to mature and give birth in the body
Researcher Lai Liangxue of Guangzhou Institute of Biomedicine and Health Research of Chinese Academy of Sciences and Chairman Mi Jidong of Beijing Sino Valley Biotech Co.
, Ltd.
are the co-corresponding authors of the published paper.
Wang Xiaomin, Liang Yanhui and Zhao Jianping are co-first authors
.
Related work has been supported by the National Key R&D Program, the Strategic Pilot Project of the Chinese Academy of Sciences, and the Guangdong Province and Guangzhou Municipal Science and Technology Programs
Paper link
Figure 1: Injection of exogenous insulin for permanent neonatal diabetes model dogs, homozygous mutant on the left, chimeric mutant on the right