title: Primary osteopathy of vertebrae in a neurofibromatosis type 1 murine model.
abstract: Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder caused by mutation of the NF1 tumor suppressor gene. Spinal deformities are common skeletal manifestations in patients with NF1. To date, the mechanism of vertebral abnormalities remains unclear because of the lack of appropriate animal models for the skeletal manifestations of NF1. In the present study, we report a novel murine NF1 model, Nf1(flox/-);Col2.3Cre(+) mice. These mice display short vertebral segments. In addition, a significant reduction in cortical and trabecular bone mass of the vertebrae was observed in Nf1(flox/-);Col2.3Cre(+) mice as measured by dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computed tomography (pQCT). Peak stress and peak load were also significantly reduced in Nf1(flox/-);Col2.3Cre(+) mice as compared to controls. Furthermore, the lumbar vertebrae showed enlargement of the inter-vertebral canal, a characteristic feature of lumbar vertebrae in NF1 patients. Finally, histologic analysis demonstrated increased numbers of osteoclasts and decreased numbers of osteoblasts in the vertebrae of Nf1(flox/-);Col2.3Cre(+) mice in comparison to controls. In summary, Nf1(flox/-);Col2.3Cre(+) mice demonstrate multiple structural and functional abnormalities in the lumbar vertebrae which recapitulate the dystrophic vertebral changes in NF1 patients. This novel murine model provides a platform to understand the cellular and molecular mechanisms underlying the pathogenesis of spinal deficits in NF1 patients.
authors: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Wei
authors: W
authors: Zhang
authors: Steven D
authors: SD
authors: Rhodes
authors: Liming
authors: L
authors: Zhao
authors: Yongzheng
authors: Y
authors: He
authors: Yingze
authors: Y
authors: Zhang
authors: Yong
authors: Y
authors: Shen
authors: Dalong
authors: D
authors: Yang
authors: Xiaohua
authors: X
authors: Wu
authors: Xiaohong
authors: X
authors: Li
authors: Xianlin
authors: X
authors: Yang
authors: Su-Jung
authors: SJ
authors: Park
authors: Shi
authors: S
authors: Chen
authors: Charles
authors: C
authors: Turner
authors: Feng-Chun
authors: FC
authors: Yang
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D016514:Genes, Neurofibromatosis 1; D051379:Mice; D018345:Mice, Knockout; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000473:pathology*; D013131:Spine / Q000473:pathology*; D014057:Tomography, X-Ray Computed