Mouse Genome Informatics
cn
    Nf1tm1Par/Nf1tm1Par
Tg(Prrx1-cre)1Cjt/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * C57BL/6N * SJL/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
skeleton
• callus following fracture shows increased number of osteoclasts; most osteoclasts are localized within fibrous tissue and not on the bone surface as in controls
• mutants exhibit delayed and defective fracture healing characterized by diminished cartilaginous callus formation, increased bone formation near the cortical bone on the periosteum but not in the fracture gap, and persistence of cartilage at day 21 such that bony bridging is not observed
• while total callus volume following fracture is larger in mutants at day 7 and 10 due to rapid initial growth of fibrous tissue (desmal type ossification), by day 14 and 21, the total callus volume is significantly smaller
• accumulation and persistence of fibrous tissue in the fracture gap, with increased numbers of osteoclasts
• increase in number of blood vessels in mutant fractures (in callus) compared to controls, indicating increased vascularization of the fracture tissue, however no osteogenesis results from this increased vascularization
• ectopic fat tissue is seen in the fracture site
• decrease of regenerative tissue bone mineral density following fracture
• dramatic cortical bone thickening following fracture
• fewer osteoblasts are seen within the fracture gap throughout healing compared to controls, however, osteoblast number is increased at the periosteal surface
• bone fractures exhibit impaired cartilage formation and increased periosteal ossification at the cortices
• presence of large areas of non-mineralized osteoid in the fracture gap, indicating decreased mineralization of the extracellular matrix
• thickening of the osteoid layer in the periosteal region following fracture
• endochondrial formation is impaired following fracture but periosteal bone formation is enhanced
• bones are weaker; femora show lower torsional stiffness and ultimate torque at failure compared to controls
• fractured bones of mutants that are allowed to heal also exhibit a lower torsional stiffness and ultimate torque at failure compared to controls

homeostasis/metabolism
• mutants exhibit delayed and defective fracture healing characterized by diminished cartilaginous callus formation, increased bone formation near the cortical bone on the periosteum but not in the fracture gap, and persistence of cartilage at day 21 such that bony bridging is not observed
• while total callus volume following fracture is larger in mutants at day 7 and 10 due to rapid initial growth of fibrous tissue (desmal type ossification), by day 14 and 21, the total callus volume is significantly smaller
• accumulation and persistence of fibrous tissue in the fracture gap, with increased numbers of osteoclasts
• increase in number of blood vessels in mutant fractures (in callus) compared to controls, indicating increased vascularization of the fracture tissue, however no osteogenesis results from this increased vascularization
• ectopic fat tissue is seen in the fracture site

hematopoietic system
• callus following fracture shows increased number of osteoclasts; most osteoclasts are localized within fibrous tissue and not on the bone surface as in controls

immune system
• callus following fracture shows increased number of osteoclasts; most osteoclasts are localized within fibrous tissue and not on the bone surface as in controls

Mouse Models of Human Disease
OMIM IDRef(s)
Neurofibromatosis, Type I; NF1 162200 J:193350