huNK2R(TACR2) Mouse

The TACR2 gene encodes tachykinin receptor 2 (also known as neurokinin 2 receptor, NK2R), a member of the G protein-coupled receptor (GPCR) superfamily that serves as a high-affinity receptor for neurokinin A (also referred to as substance K). Recent studies have shown that the TACR2/NK2R signaling pathway is closely associated with metabolic diseases such as obesity and type 2 diabetes (T2D) and plays important roles in regulating energy expenditure and appetite. NK2R agonists simultaneously promote energy expenditure and induce sustained non-aversive appetite suppression independently of the canonical leptin signaling pathway, thereby effectively reducing body weight and rapidly improving insulin sensitivity. In diet-induced obesity (DIO) mice, Ob/Ob mice, Mc4r knockout mice, and diabetic/obese cynomolgus monkey models, NK2R-selective agonists significantly reduced body weight, blood glucose, triglyceride, and cholesterol levels while improving insulin resistance, without causing any apparent severe adverse effects ^[1-2]. Therefore, as a single target capable of simultaneously regulating energy expenditure and appetite, NK2R represents a promising therapeutic target for metabolic diseases and provides a novel strategy for the development of precision therapies for obesity, type 2 diabetes (T2D), and related metabolic disorders.

The huNK2R(TACR2) humanized mouse was generated via gene-editing technology by replacing the sequence spanning from the start codon to the stop codon of the endogenous mouse Tacr2 gene with the corresponding sequence of the human TACR2 gene. Its primary applications include mechanistic studies of metabolic diseases such as obesity and type 2 diabetes (T2D), as well as the exploration of therapeutic strategies targeting the NK2R pathway. This model can also be used to evaluate the potential effects of related interventions on energy metabolism and appetite regulation.