TY - JOUR
T1 - Spontaneous fracture (sfx)
T2 - A mouse genetic model of defective peripubertal bone formation
AU - Beamer, W. G.
AU - Rosen, C. J.
AU - Bronson, R. T.
AU - Gu, W.
AU - Donahue, L. R.
AU - Baylink, D. J.
AU - Richardson, C. C.
AU - Crawford, G. C.
AU - Barker, J. E.
N1 - Funding Information:
The authors appreciate the critical reviews of the manuscript provided by Dr. K. Johnson and Dr. T. O’Brien, and the proficient technical assistance of C. Ackert and J. Burgess. This work was supported by NIH DK27726 and HL49761 (to J. E. B.), AR43618 (to W. G. B.), CA34196 (CORE support, The Jackson Laboratory), and AR45433 (to C. J. R.), and the Musculoskeletal Disease Center, J. L. Pettis VAMC, and Loma Linda University (to D. J. B.).
PY - 2000
Y1 - 2000
N2 - A new mouse model of stage-specific bone growth failure and fracture has been recovered as an autosomal recessive mutation, designated spontaneous fracture (sfx). The sfx/sfx mice are phenotypically normal until shortly after weaning, when reduced mobility and impaired somatic growth are first noted. By 6 weeks of age, body, spleen, and thymus weights, as well as hematocrits and serum calcium, inorganic phosphate, total alkaline phosphatase, insulin-like growth factor-I, and osteocalcin levels are decreased. The sfx/sfx mice also show reduced femoral cortical density and diaphyseal circumference, as well as a paucity of mature osteoblasts on bone surfaces. Histological analyses of the femur and tibia in the mutants show subtle reduction of chondrocyte numbers in epiphyseal-plate columns, reduction of matrix, and near absence of osteoid below the differentiated chondrocytes. Trabeculae in proximal tibiae, iliacs, and vertebral bodies are sparse and thin. Cortical bone thickness of mutants is markedly thinned in all sites examined. By 7-8 weeks, radiographic films routinely show spontaneous impact fractures of the distal femur accompanied by callus formation, whereas complete fractures are less commonly observed. Volumetric bone mineral density (BMD) of mutant femurs is similar to +/? littermates in the center of the femoral diaphysis, but BMD declines as either end of the femoral diaphysis is approached. We have mapped the gene responsible for this phenotype to central Chromosome 14. Reduced bone mass, impaired bone formation, abnormalities of bone architecture, and a disposition to spontaneous fracture identify sfx/sfx mice as a useful model for understanding the mechanisms responsible for peripubertal bone formation. (C) 2000 by Elsevier Science Inc.
AB - A new mouse model of stage-specific bone growth failure and fracture has been recovered as an autosomal recessive mutation, designated spontaneous fracture (sfx). The sfx/sfx mice are phenotypically normal until shortly after weaning, when reduced mobility and impaired somatic growth are first noted. By 6 weeks of age, body, spleen, and thymus weights, as well as hematocrits and serum calcium, inorganic phosphate, total alkaline phosphatase, insulin-like growth factor-I, and osteocalcin levels are decreased. The sfx/sfx mice also show reduced femoral cortical density and diaphyseal circumference, as well as a paucity of mature osteoblasts on bone surfaces. Histological analyses of the femur and tibia in the mutants show subtle reduction of chondrocyte numbers in epiphyseal-plate columns, reduction of matrix, and near absence of osteoid below the differentiated chondrocytes. Trabeculae in proximal tibiae, iliacs, and vertebral bodies are sparse and thin. Cortical bone thickness of mutants is markedly thinned in all sites examined. By 7-8 weeks, radiographic films routinely show spontaneous impact fractures of the distal femur accompanied by callus formation, whereas complete fractures are less commonly observed. Volumetric bone mineral density (BMD) of mutant femurs is similar to +/? littermates in the center of the femoral diaphysis, but BMD declines as either end of the femoral diaphysis is approached. We have mapped the gene responsible for this phenotype to central Chromosome 14. Reduced bone mass, impaired bone formation, abnormalities of bone architecture, and a disposition to spontaneous fracture identify sfx/sfx mice as a useful model for understanding the mechanisms responsible for peripubertal bone formation. (C) 2000 by Elsevier Science Inc.
KW - Bone formation
KW - Mice
KW - Mutation
KW - Spontaneous fracture
UR - http://www.scopus.com/inward/record.url?scp=0033766293&partnerID=8YFLogxK
U2 - 10.1016/S8756-3282(00)00369-0
DO - 10.1016/S8756-3282(00)00369-0
M3 - Article
C2 - 11062347
AN - SCOPUS:0033766293
SN - 8756-3282
VL - 27
SP - 619
EP - 626
JO - Bone
JF - Bone
IS - 5
ER -