Mouse Models of Tumor Development in Neurofibromatosis Type 1

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Abstract
Neurofibromatosis type 1 (NF1) is a prevalent familial cancer syndrome resulting from germ line mutations in theNF1tumor suppressor gene. Hallmark features of the disease are the development of benign peripheral nerve sheath tumors (neurofibromas), which can progress to malignancy. Unlike humans, mice that are heterozygous for a mutation inNf1do not develop neurofibromas. However, as described here, chimeric mice composed in part ofNf1−/−cells do, which demonstrates that loss of the wild-typeNf1allele is rate-limiting in tumor formation. In addition, mice that carry linked germ line mutations inNf1andp53develop malignant peripheral nerve sheath tumors (MPNSTs), which supports a cooperative and causal role for p53 mutations in MPNST development. These two mouse models provide the means to address fundamental aspects of disease development and to test therapeutic strategies.