November 18, 2011

Skeletal defects in genetic disorder

A new mouse model provides a tool for testing novel therapeutic approaches for neurofibromatosis.


Neurofibromatosis type I, an inherited disorder caused by mutations in the NF1 gene, is characterized by nerve tissue and optic pathway tumors and by other clinical features including skeletal abnormalities. In an effort to understand how NF1 mutations cause bone lesions, Florent Elefteriou and colleagues generated a mouse model lacking the NF1 gene in the progenitor cells that give rise to the limbs and axial (central) skeleton.

They report in the Oct. 15 issue of Human Molecular Genetics that mice missing NF1 in these progenitor cells have bone defects that are similar to patients with neurofibromatosis. They also demonstrate that a drug that blocks the RAS/ERK signaling pathway, which is activated in the absence of NF1, rescues a bone porosity defect in the mice.

The study provides a new mouse preclinical model for testing novel therapeutic approaches for neurofibromatosis and suggests that the RAS/ERK signaling pathway is a rational target for prevention of bony lesions in the disorder.

This research was supported with funding from the Department of Defense, the National Institute of Arthritis and Musculoskeletal and Skin Disease, and the Children’s Tumor Foundation.