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PLoS One. 2015 Mar 18;10(3):e0119093. doi: 10.1371/journal.pone.0119093. eCollection 2015.

Dystrophic spinal deformities in a neurofibromatosis type 1 murine model.

Author information

1
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
2
Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Hebei Medical University, The Third Hospital, Shijiazhuang, China.
3
Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
4
Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
5
Department of Endocrinology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
6
Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland, United States of America.
7
Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, California, United States of America.
8
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

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.

PMID:
25786243
PMCID:
PMC4364663
DOI:
10.1371/journal.pone.0119093
[Indexed for MEDLINE]
Free PMC Article

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