Ntsr1-KO Mouse

Ntsr1, short for neurotensin receptor 1, is a G protein-coupled receptor (GPCR) [1,2]. It is involved in various biological processes, such as regulating cell-signaling events through the canonical activation of G proteins and engagement of β-arrestins [1]. Ntsr1 is also associated with pathways like JAK2-STAT3-Thbs1 [2], and its activation can lead to endoplasmic reticulum stress response via ATF6 activation [2].

In animal models, a β-arrestin-biased allosteric modulator of Ntsr1, SBI-553, selectively attenuates addictive behaviors without the severe side effects of traditional Ntsr1 agonists, indicating that Ntsr1 G protein and β-arrestin activation produce distinct physiological effects [1]. In pulmonary hypertension (PH) rat models, Ntsr1 contributes to PH development by enhancing endoplasmic reticulum stress via the JAK2-STAT3-Thbs1 signaling pathway, and knockdown of Ntsr1 in rats can reverse the PH phenotype [2]. In lung cancer cell models, knockdown of Ntsr1 inhibits cancer cell migration and invasion, and in lung adenocarcinoma, it promotes epithelial-mesenchymal transition and metastasis through the Wnt/β-catenin pathway [3,4]. In gastric adenocarcinoma cells, Ntsr1 shRNA reduces cell proliferation and invasion, and Ntsr1 interacts with MET via PIK3CA to modulate cell invasion ability [5].

In conclusion, Ntsr1 plays crucial roles in multiple biological processes and disease conditions. Gene-knockout or conditional-knockout mouse models and other loss-of-function experiments have revealed its significant impact on addictive behaviors, pulmonary hypertension, lung cancer, and gastric adenocarcinoma. Understanding Ntsr1's functions provides potential therapeutic strategies for these diseases [1,2,3,4,5].