Development of craniofacial structures in transgenic mice with constitutively active PTH/PTHrP receptor.
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.
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department Health Human Services, Bethesda, MD 20892, USA. ryuryu@tokyo.ndu.ac.jp
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Tsutsui
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Riminucci
Kenn
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Holmbeck
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Bianco
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Robey
D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000000981:diagnostic imaging / Q000196:embryology / Q000378:metabolism; D005147:Facial Bones / Q000000981:diagnostic imaging / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014057:Tomography, X-Ray Computed
D024042:Collagen Type I; D010281:Parathyroid Hormone