Disruption of the Flnb gene in mice phenocopies the human disease spondylocarpotarsal synostosis syndrome

Claire Farrington-Rock, Veneta Kirilova, Lisa Dillard-Telm, Alexander D Borowsky, Sara Chalk, Matthew J. Rock, Daniel H. Cohn, Deborah Krakow

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Spondylocarpotarsal synostosis syndrome (SCT) is an autosomal recessive disease that is characterized by short stature, and fusions of the vertebrae and carpal and tarsal bones. SCT results from homozygosity or compound heterozygosity for nonsense mutations in FLNB. FLNB encodes filamin B, a multifunctional cytoplasmic protein that plays a critical role in skeletal development. Protein extracts derived from cells of SCT patients with nonsense mutations in FLNB did not contain filamin B, demonstrating that SCT results from absence of filamin B. To understand the role of filamin B in skeletal development, an Flnb- mouse model was generated. The Flnb-/- mice were phenotypically similar to individuals with SCT as they exhibited short stature and similar skeletal abnormalities. Newborn Flnb- mice had fusions between the neural arches of the vertebrae in the cervical and thoracic spine. At postnatal day 60, the vertebral fusions were more widespread and involved the vertebral bodies as well as the neural arches. In addition, fusions were seen in sternum and carpal bones. Analysis of the Flnb- mice phenotype showed that an absence of filamin B causes progressive vertebral fusions, which is contrary to the previous hypothesis that SCT results from failure of normal spinal segmentation. These findings suggest that spinal segmentation can occur normally in the absence of filamin B, but the protein is required for maintenance of intervertebral, carpal and sternal joints, and the joint fusion process commences antenatally.

Original languageEnglish (US)
Pages (from-to)631-641
Number of pages11
JournalHuman Molecular Genetics
Issue number5
StatePublished - Mar 1 2008

ASJC Scopus subject areas

  • Genetics


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