Pth1r, the type 1 parathyroid hormone receptor, is a G protein-coupled receptor that plays a crucial role in mineral ion homeostasis and bone metabolism. It is a key regulator in the signaling pathways of parathyroid hormone (PTH) and PTH-related protein (PTHrP), which activate adenylyl cyclase through Pth1r, especially in cells of the osteoblast lineage [1]. This receptor is also involved in other biological processes like cardiovascular homeostasis, immune regulation in the male reproductive system, and cranial base development [2,3,4]. Genetic models, such as KO/CKO mouse models, have been instrumental in understanding its functions.

In cranial base development, Gli1-CreERT2;Pth1rfl/fl;Tomatofl/+ mice showed a shortened cranial base and premature synchondrosis closure, indicating Pth1r signaling in Gli1-positive cells is essential for postnatal development and maintenance of cranial base synchondroses [4]. In neural crest cells, Wnt1-Cre;Pth1rfl/fl;Tomatofl/+ mice had short snouts, jaws, and abnormal nasal cartilage differentiation, suggesting Pth1r in neural crest cells regulates nasal cartilage development [5]. Mice with Pth1r deletion in Prx1-positive mesenchymal cells (Prx1Cre;PTH1Rfl/fl) exhibited decreased alveolar bone mass due to apoptotic response activation, uncovering the anti-apoptotic function of Pth1r in mesenchymal progenitors during mandibular growth [6].

In conclusion, Pth1r is vital for multiple biological processes, including bone metabolism, cranial and nasal cartilage development, and mandibular growth. Gene-knockout and conditional-knockout mouse models have significantly contributed to understanding its role in these processes and related disease conditions, such as those affecting the skeletal and male reproductive systems. This knowledge can potentially lead to new therapeutic strategies for associated diseases.