Tsutsui T W, Riminucci M, Holmbeck Kenn, Bianco P, Robey P G
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department Health Human Services, Bethesda, MD 20892, USA.
Bone. 2008 Feb;42(2):321-31. doi: 10.1016/j.bone.2007.09.057. Epub 2007 Oct 16.
Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) regulate calcium homeostasis, and PTHrP further regulates growth and development. A transgenic mouse carrying the constitutively active PTH/PTHrP receptor (HKrk-H223R) under the control of the mouse bone and odontoblast-specific alpha1(I) collagen promoter (Col1-caPPR) has been developed to demonstrate the complex actions of this mutant receptor in hard tissue formation. We have further characterized Col1-caPPR mice abnormalities in the craniofacial region as a function of development. Col1-caPPR mice exhibited a delay in embryonic bone formation, followed by expansion of a number of craniofacial bones including the maxilla and mandible, delay in tooth eruption and teratosis, and a disrupted temporomandibular joint (TMJ). These findings suggest that the Col1-caPPR mouse is a useful model for characterization of the downstream effects of the constitutively active receptor during development and growth, and as a model for development of treatments of human diseases with similar characteristics.
甲状旁腺激素（PTH）和甲状旁腺激素相关肽（PTHrP）调节钙稳态，并且PTHrP进一步调节生长和发育。已构建了一种转基因小鼠，其在小鼠骨和成牙本质细胞特异性α1（I）胶原启动子（Col1-caPPR）的控制下携带组成型活性PTH/PTHrP受体（HKrk-H223R），以证明该突变受体在硬组织形成中的复杂作用。我们进一步将Col1-caPPR小鼠颅面区域的异常表征为发育的函数。Col1-caPPR小鼠表现出胚胎骨形成延迟，随后包括上颌骨和下颌骨在内的一些颅面骨扩大，牙齿萌出延迟和畸形，以及颞下颌关节（TMJ）紊乱。这些发现表明，Col1-caPPR小鼠是用于表征发育和生长过程中组成型活性受体的下游效应的有用模型，并且作为具有相似特征的人类疾病治疗开发的模型。
