Previous research has determined that neurofibromas result from a mutation in a gene (called Nf1), which normally acts as a tumor suppressor by producing a complex protein called neurofibromin to help regulate cell growth. Mutation of the Nf1 gene inhibits neurofibromin production, leading to irregular cell growth and possible tumor development. Dr. Ratner and her colleagues suggest in their study that the timing of this gene mutation is critical to whether neurofibroma tumors form.

In one set of experiments, the researchers worked with genetically engineered nerve root cells from embryonic mice. They discovered that mutating both of two mouse Nf1 genes at 12.5 days after conception (a critical stage in mouse embryonic development when cells that eventually differentiate to form the nervous system are just getting ready to do so) would create cell colonies. Experiments. researchers van In another set of worked with mice that were engineered for genetically expression of a gene called Desert only using a genetic trick to cause Nf1 mutation van de Egel (Dhh) in cells that express that gene. Again, the researchers discovered that by mutating both Nf1 genes at 12.5 days post conception in developing nerve cells, the resulting adult mice developed neurofibromas and had shorter life spans than their littermates whose genes were not mutated. If the mutations occurred earlier or later than 12.5 days, in both sets of experiments neurofibroma cells did not begin to form.

Dr. Ratner and her colleagues report that because nerves from patients with Neurofibromatosis type-1 have not been analyzed, direct comparisons between disease formation in humans and mice can not yet be made.

Neurofibromatosis 1 is an autosomal dominant inherited disease, which means the gene mutation only needs to occur in one chromosome for a person to get the disease. Disease symptoms may be evident at birth, during infancy and almost always by the time a child is 10 years old. The condition affects one of every 3,000 people worldwide with nearly 90 percent of the patients developing neurofibromas. Many NF1 patients conduct normal lives with the disease, with the primary manifestation being numerous soft brown pigment spots on the skin, and numerous tumors that are very small under the skin. Other patients, however, develop learning disabilities, scoliosis, and benign brain tumors as children, and are at risk for cardiovascular problems and malignant tumors as adults. Cincinnati Children's has a leading multi-disciplinary clinic for diagnosis and management of NF1.

The study included researchers from the Hoxworth Blood Center, University of Cincinnati College of Medicine; Departments of Pathology at Massachusetts General Hospital and Harvard Medical School (Boston) and the Departments of Cell Biology and Genetics at Erasmus University Medical Center (Rotterdam, Netherlands). Also offering assistance through provision of genetically engineered mice and other materials were the University of Texas Southwestern, the Stowers Institute and Rockefeller University. Funding support came from the National Institutes of Health.

Cincinnati Children's, one of the top five children's hospitals in the nation according to Child magazine, is a 475bed institution devoted to bringing the world the joy of healthier kids. Cincinnati Children's is dedicated to providing care that is timely, efficient, effective, family-centered, equitable and safe. For its efforts to transform the way healthcare is provided, Cincinnati Children's received the 2006 American Hospital Association-McKesson Quest for Quality Prize®. Cincinnati Children's ranks second nationally among all pediatric centers in research grants from the National Institutes of Health and is a teaching affiliate of the University of Cincinnati College of Medicine. The Cincinnati Children's vision is to be the leader in improving child health.