Study On The Function Of Protein Tyrosine Phosphatase PTP1B Mutant Using Mouse Model

With the progress of the times,the conditions of human life have been greatly improved.Because of the abundance of food and the intelligence of work,the pressure of human survival can be almost ignored.Diabetes and obesity,which are threats to human health,are accompanied by the intake of a large number of high-calorie foods and the low level of exercise.Patients are accompanied by varying degrees of obesity in the early stage of the diabetes,and the risk of diabetes in obese people is also greater than the normal weight people.Diabetes and obesity patients are also at high risk of cardiovascular diseases,and may also suffer from chronic damage of organs and tissues,such as chronic kidney disease,arthritis,eye diseases,etc.Prolonged illness will directly threaten their lives.How to prevent and treat diabetes and control weight scientifically have become a global hot research topic.The main influencing factor of diabetes and obesity is the energy metabolism imbalance caused by dietary habits and organ diseases,and diabetes and obesity are characterized by persistent hyperglycemia.Obese people with normal physical function can lose weight simply by controlling their diet,cutting calories and increasing physical activity.The pathological mechanism of obesity and diabetes caused by abnormal physiological function will be the focus of our research.Tyrosyl phosphorylation of proteins is fundamental to the maintenance of many cellular functions,including gene expression,cell growth,differentiation,migration,adhesion,and apoptosis.The level of net phosphorylation of protein tyrosyl phosphate residues in cells is regulated by the phosphorylation of protein tyrosine kinase(PTK)and the dephosphorylation of protein tyrosine phosphatase(PTP).Maintaining homeostasis control of tyrosyl phosphorylation in cells is extremely important,and disorders in these processes often lead to the development of a variety of pathophysiological conditions,including cancer,metabolic,neuronal,and immune diseases.In the PTP family,PTP1 B is a key therapeutic target associated with type 2 diabetes mellitus(T2DM)and the treatment of obesity.The focus of this study is to apply the gene mutation mouse model to study the effect of the inactivation of PTP1 B catalytic activity site on the blood glucose level of mice and the mechanism of action,so as to further explain the physiological function of PTP1 B.We used CRISPR/Cas9 to obtain two genetically modified mice with PTP1 B active site mutations.It has been proved that PTP1 B has a negative regulation effect on the insulin signaling pathway,and the mutation of PTP1 B active site will lead to increased insulin sensitivity in mouse cells,by the observation of mouse phenotype,weight analysis,glucose tolerance type experiment,insulin sensitivity experiment,and observation of tissue sections,Western blot,etc.After a long period of observation,it was not found that the two point mutations of C215 S and D181 A had any negative effects on mice,including epigenetic morphology and visceral organ tissue.Mutant mice can grow and reproduce normally,and there is no difference between living state and wild type.After a long period of monitoring model mouse weight found mutant mice have the advantage of reducing the risk of obesity.When model mice were stimulated by the outside world,such as intraperitoneal injections of glucose or insulin,mutant mice had higher insulin sensitivity than wild mice,and more directly explained that PTP1 B played a negative regulatory role in the process of lowering blood sugar.Although epigenetic traits and visceral tissue do not exhibit adverse or good differences,there is no doubt about the important role of PTP1 B in insulin signaling pathways and leptin signaling pathways,and we need to pay close attention to the indicators of mutant mice and look forward to new discoveries.