New Mouse Model for Neurofibromatosis

Researchers have found that inactivation of the NF1 gene, which codes for neurofibromin, a protein that suppresses the ras oncogene, causes defects in the development of both the neural crest and of cardiovascular tissues. These findings were published December 9, 2002, in the online edition of Nature Genetics.

Inactivation of NF1, which occurs in about 1 in 4000 births, causes neurofibromatosis type 1 (NF1) or von Recklinghausen neurofibromatosis, which are characterized by benign and malignant tumors. By not inactivating the ras oncogene, this defect also results in the overproduction of the NFATc1 protein, which is related to heart valve development.

Previously it had not been possible to produce a mouse model for this disease because developmental defects in the cardiovascular system prevented the mouse embryos from reaching full term. To circumvent this problem, researchers from the University of Pennsylvania School of Medicine (Philadelphia, USA; www.upenn.edu) engineered a mouse line that expressed the NF1 deficiency in the neural crest but not in the endothelial cells that form the developing cardiovascular system. Mice from this line survived to birth and then developed tumors typical of neurofibromatosis.

"Our work shows that the Nf1 gene blocks the ras oncogene for different purposes in the different cell types,” explained Dr. Jonathan A. Epstein, associate professor in the cardiovascular division of the University of Pennsylvania department of medicine. "In endothelial cells, we see a possibility to mitigate some of the harm done by the loss of Nf1 by blocking the excessive amounts of NFATc1 protein. The more we learn about the mechanisms behind type 1 Neurofibromatosis, the better our options for treating the disease.”



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