Dystrophic spinal deformities in a neurofibromatosis type 1 murine model

Steven D. Rhodes, Wei Zhang, Dalong Yang, Hao Yang, Shi Chen, Xiaohua Wu, Xiaohong Li, Xianlin Yang, Khalid S. Mohammad, Theresa A. Guise, Amanda L. Bergner, David A. Stevenson, Feng Chun Yang

Research output: Contribution to journalArticle

Abstract

Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/-;PeriCre and Nf1flox/-;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36-60% of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population.

Original languageEnglish (US)
Article numbere0119093
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 18 2015

Fingerprint

Neurofibromatosis 1
Fusion reactions
animal models
intervertebral disks
Intervertebral Disc
Defects
Bone
mice
bones
scoliosis
Bone Remodeling
Scoliosis
spine (bones)
pathophysiology
human diseases
Population
morbidity
Spine
pathogenesis
case studies

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Rhodes, S. D., Zhang, W., Yang, D., Yang, H., Chen, S., Wu, X., ... Yang, F. C. (2015). Dystrophic spinal deformities in a neurofibromatosis type 1 murine model. PLoS One, 10(3), [e0119093]. https://doi.org/10.1371/journal.pone.0119093

Dystrophic spinal deformities in a neurofibromatosis type 1 murine model. / Rhodes, Steven D.; Zhang, Wei; Yang, Dalong; Yang, Hao; Chen, Shi; Wu, Xiaohua; Li, Xiaohong; Yang, Xianlin; Mohammad, Khalid S.; Guise, Theresa A.; Bergner, Amanda L.; Stevenson, David A.; Yang, Feng Chun.

In: PLoS One, Vol. 10, No. 3, e0119093, 18.03.2015.

Research output: Contribution to journalArticle

Rhodes, SD, Zhang, W, Yang, D, Yang, H, Chen, S, Wu, X, Li, X, Yang, X, Mohammad, KS, Guise, TA, Bergner, AL, Stevenson, DA & Yang, FC 2015, 'Dystrophic spinal deformities in a neurofibromatosis type 1 murine model', PLoS One, vol. 10, no. 3, e0119093. https://doi.org/10.1371/journal.pone.0119093
Rhodes SD, Zhang W, Yang D, Yang H, Chen S, Wu X et al. Dystrophic spinal deformities in a neurofibromatosis type 1 murine model. PLoS One. 2015 Mar 18;10(3). e0119093. https://doi.org/10.1371/journal.pone.0119093
Rhodes, Steven D. ; Zhang, Wei ; Yang, Dalong ; Yang, Hao ; Chen, Shi ; Wu, Xiaohua ; Li, Xiaohong ; Yang, Xianlin ; Mohammad, Khalid S. ; Guise, Theresa A. ; Bergner, Amanda L. ; Stevenson, David A. ; Yang, Feng Chun. / Dystrophic spinal deformities in a neurofibromatosis type 1 murine model. In: PLoS One. 2015 ; Vol. 10, No. 3.
@article{2e16e0ba00454f30be5302b769588fa8,
title = "Dystrophic spinal deformities in a neurofibromatosis type 1 murine model",
abstract = "Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/-;PeriCre and Nf1flox/-;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36-60{\%} of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population.",
author = "Rhodes, {Steven D.} and Wei Zhang and Dalong Yang and Hao Yang and Shi Chen and Xiaohua Wu and Xiaohong Li and Xianlin Yang and Mohammad, {Khalid S.} and Guise, {Theresa A.} and Bergner, {Amanda L.} and Stevenson, {David A.} and Yang, {Feng Chun}",
year = "2015",
month = "3",
day = "18",
doi = "10.1371/journal.pone.0119093",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Dystrophic spinal deformities in a neurofibromatosis type 1 murine model

AU - Rhodes, Steven D.

AU - Zhang, Wei

AU - Yang, Dalong

AU - Yang, Hao

AU - Chen, Shi

AU - Wu, Xiaohua

AU - Li, Xiaohong

AU - Yang, Xianlin

AU - Mohammad, Khalid S.

AU - Guise, Theresa A.

AU - Bergner, Amanda L.

AU - Stevenson, David A.

AU - Yang, Feng Chun

PY - 2015/3/18

Y1 - 2015/3/18

N2 - Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/-;PeriCre and Nf1flox/-;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36-60% of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population.

AB - Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/-;PeriCre and Nf1flox/-;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36-60% of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population.

UR - http://www.scopus.com/inward/record.url?scp=84925431346&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925431346&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0119093

DO - 10.1371/journal.pone.0119093

M3 - Article

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e0119093

ER -