Development of craniofacial structures in transgenic mice with constitutively active PTH/PTHrP receptor

TY - JOUR

T1 - Development of craniofacial structures in transgenic mice with constitutively active PTH/PTHrP receptor

AU - Tsutsui, T W

AU - Riminucci, M

AU - Holmbeck, Kenn

AU - Bianco, P

AU - Robey, P G

PY - 2008/2

Y1 - 2008/2

N2 - 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.

AB - 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.

KW - Animals

KW - Collagen Type I/genetics

KW - Embryo, Mammalian/diagnostic imaging

KW - Facial Bones/diagnostic imaging

KW - Female

KW - Male

KW - Mice

KW - Mice, Transgenic

KW - Microscopy, Electron, Scanning

KW - Parathyroid Hormone/genetics

KW - Promoter Regions, Genetic/genetics

KW - Tomography, X-Ray Computed

U2 - 10.1016/j.bone.2007.09.057

DO - 10.1016/j.bone.2007.09.057

M3 - Journal article

C2 - 18063434

SN - 8756-3282

VL - 42

SP - 321

EP - 331

JO - Bone

JF - Bone

IS - 2

ER -