Osr2, or odd-skipped related 2, is a zinc-finger containing transcription factor. It is involved in multiple biological processes, including the development of craniofacial structures, limbs, kidneys, teeth, and the secondary palate. It also plays a role in osteoblast proliferation and differentiation, and is associated with pathways such as BMP and Sema3 signaling [2,3,4,7]. Gene knockout (KO) mouse models have been crucial in understanding its functions [2,3,5,7].

In KO mouse models, deletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, suggesting it acts as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumors [1]. In palate development, Osr2-/-mice show impaired palatal shelf growth and cleft palate due to reduced palatal mesenchyme proliferation [7]. In tooth development, Osr2-/-mice have supernumerary teeth, and Osr2 acts downstream of Pax9, interacting with Msx1 and Pax9 to pattern the tooth developmental field [3]. Also, deletion of Osr2 partially rescues tooth development in Runx2 mutant mice [5]. In addition, MAX deficiency in human endometrial stromal cells impairs decidualization by down-regulating OSR2, as seen in women with recurrent spontaneous abortion [6].

In conclusion, Osr2 is a key regulator in multiple developmental processes and disease-related cellular functions. KO mouse models have been instrumental in revealing its roles in cancer immunotherapy-related T cell exhaustion, palate and tooth development, as well as endometrial decidualization, providing insights into potential therapeutic targets for related diseases.