title: Mouse models of tumor development in neurofibromatosis type 1.
abstract: Neurofibromatosis type 1 (NF1) is a prevalent familial cancer syndrome resulting from germ line mutations in the NF1 tumor 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 in Nf1 do not develop neurofibromas. However, as described here, chimeric mice composed in part of Nf1-/- cells do, which demonstrates that loss of the wild-type Nf1 allele is rate-limiting in tumor formation. In addition, mice that carry linked germ line mutations in Nf1 and p53 develop 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.
authors.affiliation: Department of Biology and Center for Cancer Research and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: K
authors.initials: K
authors.lastname: Cichowski
authors.forename: T S
authors.initials: TS
authors.lastname: Shih
authors.forename: E
authors.initials: E
authors.lastname: Schmitt
authors.forename: S
authors.initials: S
authors.lastname: Santiago
authors.forename: K
authors.initials: K
authors.lastname: Reilly
authors.forename: M E
authors.initials: ME
authors.lastname: McLaughlin
authors.forename: R T
authors.initials: RT
authors.lastname: Bronson
authors.forename: T
authors.initials: T
authors.lastname: Jacks
mesh_terms: D000818:Animals; D002460:Cell Line; D002678:Chimera; D004195:Disease Models, Animal; D005260:Female; D016514:Genes, Neurofibromatosis 1; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D018317:Nerve Sheath Neoplasms / Q000235:genetics* / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000473:pathology*; D025542:Neurofibromin 1; D011506:Proteins / Q000032:analysis / Q000502:physiology; D009418:S100 Proteins / Q000032:analysis; D012583:Schwann Cells / Q000737:chemistry / Q000648:ultrastructure; D013234:Stem Cells
chemical_list: D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1; D011506:Proteins; D009418:S100 Proteins