RGD Reference Report - Craniosynostosis in transgenic mice overexpressing Nell-1. - Rat Genome Database

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Craniosynostosis in transgenic mice overexpressing Nell-1.

Authors: Zhang, X  Kuroda, S  Carpenter, D  Nishimura, I  Soo, C  Moats, R  Iida, K  Wisner, E  Hu, FY  Miao, S  Beanes, S  Dang, C  Vastardis, H  Longaker, M  Tanizawa, K  Kanayama, N  Saito, N  Ting, K 
Citation: Zhang X, etal., J Clin Invest 2002 Sep;110(6):861-70.
RGD ID: 633405
Pubmed: PMID:12235118   (View Abstract at PubMed)
PMCID: PMC151127   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI15375   (Journal Full-text)

Previously, we reported NELL-1 as a novel molecule overexpressed during premature cranial suture closure in patients with craniosynostosis (CS), one of the most common congenital craniofacial deformities. Here we describe the creation and analysis of transgenic mice overexpressing Nell-1. Nell-1 transgenic animals exhibited CS-like phenotypes that ranged from simple to compound synostoses. Histologically, the osteogenic fronts of abnormally closing/closed sutures in these animals revealed calvarial overgrowth and overlap along with increased osteoblast differentiation and reduced cell proliferation. Furthermore, anomalies were restricted to calvarial bone, despite generalized, non-tissue-specific overexpression of Nell-1. In vitro, Nell-1 overexpression accelerated calvarial osteoblast differentiation and mineralization under normal culture conditions. Moreover, Nell-1 overexpression in osteoblasts was sufficient to promote alkaline phosphatase expression and micronodule formation. Conversely, downregulation of Nell-1 inhibited osteoblast differentiation in vitro. In summary, Nell-1 overexpression induced calvarial overgrowth resulting in premature suture closure in a rodent model. Nell-1, therefore, has a novel role in CS development, perhaps as part of a complex chain of events resulting in premature suture closure. On a cellular level, Nell-1 expression may modulate and be both sufficient and required for osteoblast differentiation.



Disease Annotations    
craniosynostosis  (IMP,ISO)

Gene Ontology Annotations    

Biological Process

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Nell1  (neural EGFL like 1)

Genes (Mus musculus)
Nell1  (NEL-like 1)

Genes (Homo sapiens)
NELL1  (neural EGFL like 1)


Additional Information