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.
Tsutsui
T W
TW
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
Riminucci
M
M
Holmbeck
Kenn
K
Bianco
P
P
Robey
P G
PG
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