Study results from National Institute of Diabetes broaden understanding of RNA research
2007 NOV 12 -- Research findings, 'RNA interference and inhibition of MEK-ERK signaling prevent abnormal skeletal phenotypes in a mouse model of craniosynostosis,' are discussed in a new report. According to recent research published in the journal Nature Genetics, "Premature fusion of one or more of the cranial sutures (craniosynostosis) in humans causes over 100 skeletal diseases, which occur in 1 of approximately 2,500 live births. Among them is Apert syndrome, one of the most severe forms of craniosynostosis, primarily caused by missense mutations leading to amino acid changes S252W or P253R in fibroblast growth factor receptor 2 (FGFR2)." "Here we show that a small hairpin RNA targeting the dominant mutant form of Fgfr2 (Fgfr2(S252W)) completely prevents Apert-like syndrome in mice. Restoration of normal FGFR2 signaling is manifested by an alteration of the activity of extracellular signal-regulated kinases 1 and 2 (ERK1/2), implicating the gene encoding ERK and the genes downstream of it in disease expressivity. Furthermore, treatment of the mutant mice with U0126, an inhibitor of mitogen-activated protein (MAP) kinase kinase 1 and 2 (MEK1/2) that blocks phosphorylation and activation of ERK1/2, significantly inhibits craniosynostosis," wrote V. Shukla and colleagues, National Institute of Diabetes. The researchers concluded: "These results illustrate a pathogenic role for ERK activation in craniosynostosis resulting from FGFR2 with the S252W substitution and introduce a new concept of small-molecule inhibitor-mediated prevention and therapy for diseases caused by gain-of-function mutations in the human genome." Shukla and colleagues published their study in Nature Genetics (RNA interference and inhibition of MEK-ERK signaling prevent abnormal skeletal phenotypes in a mouse model of craniosynostosis. Nature Genetics, 2007;39(9):1145-50). For additional information, contact V. Shukla, US National Institutes of Health, Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, 10 Center Drive, Bethesda, Maryland 20892 USA.. The publisher's contact information for the journal Nature Genetics is: Nature Publishing Group, 345 Park Avenue South, New York, NY 10010-1707, USA. Keywords: United States, Bethesda, Acrocephalosyndactylia, Apert Syndrome, Biotechnology, Craniofacial, Craniosynostosis, Gene Therapy, Genetics, Neurology, Neurosurgery, RNA Research, Treatment. This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.
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