Fgfr3, fibroblast growth factor receptor 3, is a transmembrane kinase protein. It functions in regulating bone growth, expressed in chondrocytes and mature osteoblasts [3]. The FGFR3-related signaling pathway is involved in multiple biological processes, and its dysregulation is associated with various diseases, highlighting its biological importance [4]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

Mutations in Fgfr3 cause achondroplasia, the most common form of dwarfism in humans, and related chondrodysplasia syndromes [3]. These mutations increase signaling through multiple mechanisms, paradoxically suppressing growth plate chondrocyte proliferation and maturation, leading to decreased bone elongation [3]. FGFR3-TACC3 fusion, prevalent in 3-4% of human glioblastoma, activates FGFR3 kinase signaling, promoting cell proliferation and tumor progression [1]. FGFR3 mutations occur in up to half of bladder cancers, playing a role in tumorigenesis and influencing responses to immune checkpoint inhibitors [2]. FGFR3 overexpression in metastatic colorectal cancer is associated with an unfavorable prognosis [5]. In ovarian cancer, FGFR3 overexpression promotes cisplatin-resistance by phosphorylating EGFR and activating the PI3K/AKT pathway [6].

In conclusion, Fgfr3 is crucial for bone growth regulation. Studies using KO/CKO mouse models could potentially further clarify its role in bone-related diseases like achondroplasia. Its dysregulation also significantly contributes to various cancers, such as glioblastoma, bladder, colorectal, and ovarian cancers, making it an important target for potential therapeutic interventions.