Nf1 gene targeting: toward models and mechanisms.

Patients with neurofibromatosis type I develop multiple benign nerve sheath tumors and are predisposed to a number of malignancies. Since loss-of-function mutations in the NF1 gene appear to be responsible for the disease, NF1 has been classified as a tumor suppressor. Several strategies involving the targeted disruption of the murine homologue have been used in an attempt to establish an animal model for the disease and four types of animals have been generated: (1) Nf1 +/- animals, (2) NF1 -/- embryos, (3) Nf1 -/- chimeras, and (4) mice transplanted with Nf1 -/- hematopoietic stem cells. In addition to yielding mice which mimic various aspects of the human disease, each of these approaches has contributed to a better understanding of the normal function of Nf1.