Phenotypes Associated with This Genotype

Genotype
MGI:5493228

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * C57BL/6N * SJL/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

skeleton

increased osteoclast cell number ( J:193350 )

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

abnormal bone healing ( J:193350 )

• 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

decreased bone mineral density ( J:193350 )

• decrease of regenerative tissue bone mineral density following fracture

increased compact bone volume ( J:193350 )

• dramatic cortical bone thickening following fracture

abnormal osteoblast cell number ( J:193350 )

• fewer osteoblasts are seen within the fracture gap throughout healing compared to controls, however, osteoblast number is increased at the periosteal surface

abnormal cartilage morphology ( J:193350 )

• bone fractures exhibit impaired cartilage formation and increased periosteal ossification at the cortices

abnormal osteoid morphology ( J:193350 )

• presence of large areas of non-mineralized osteoid in the fracture gap, indicating decreased mineralization of the extracellular matrix

increased osteoid thickness ( J:193350 )

• thickening of the osteoid layer in the periosteal region following fracture

abnormal endochondral bone ossification ( J:193350 )

• endochondrial formation is impaired following fracture but periosteal bone formation is enhanced

fragile skeleton ( J:193350 )

• 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

abnormal bone healing ( J:193350 )

• 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

increased osteoclast cell number ( J:193350 )

• 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

increased osteoclast cell number ( J:193350 )

• 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		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:193350