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Gene Review

Nf1  -  neurofibromatosis 1

Mus musculus

Synonyms: AW494271, E030030H24Rik, Neurofibromatosis-related protein NF-1, Neurofibromin, Nf-1, ...
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Disease relevance of Nf1


Psychiatry related information on Nf1


High impact information on Nf1


Chemical compound and disease context of Nf1


Biological context of Nf1


Anatomical context of Nf1


Associations of Nf1 with chemical compounds

  • Recently neurofibromin, the protein encoded by NF1, was shown to negatively regulate Ras activity in Nf1-/- murine myeloid hematopoietic cells in vitro through the c-kit receptor tyrosine kinase (dominant white spotting, W) [23].
  • Therefore, these results demonstrate that lovastatin may prove useful in the treatment of Neurofibromatosis Type 1 [9].
  • Cyclophosphamide exposure cooperated strongly with heterozygous inactivation of Nf1 in myeloid leukemogenesis, while etoposide did not [27].
  • Ex vivo, Nf1 heterozygosity was associated with increased inducible osteoclasts in PTH-treated bone marrow cells and impairment of the actin stress fiber and cyclic adenosine monophosphate response to PTH in osteoprogenitors [28].
  • The NF2 protein merlin belongs to the band 4.1 family of proteins that link membrane proteins to the cytoskeleton and are thought to be involved in dynamic cytoskeletal reorganization [29].

Physical interactions of Nf1


Regulatory relationships of Nf1


Other interactions of Nf1

  • Nf1 and Gmcsf interact in myeloid leukemogenesis [3].
  • Hyperactivation of p21(ras) and the hematopoietic-specific Rho GTPase, Rac2, cooperate to alter the proliferation of neurofibromin-deficient mast cells in vivo and in vitro [34].
  • In contrast, we found a low incidence of neural tube defects in heterozygous Splotch mice that also harbored a mutation in one Nf1 allele [35].
  • Remarkably, U0126, an inhibitor of ERK activation, at doses which reduced the hyperactive pERK levels in NF1(+/-) mice to the levels observed in control mice, caused a reduction in the deficits in early-phase LTP and completely rescued the long-term LTP deficits [36].
  • We report that in contrast to the narrow spectrum of benign tumors in human NF2 patients, Nf2 heterozygous mice develop a variety of malignant tumors [37].

Analytical, diagnostic and therapeutic context of Nf1

  • To study the function of NF1 in normal development and to try and develop a mouse model of NF1 disease, we have used gene targeting in ES cells to generate mice carrying a null mutation at the mouse Nf1 locus [38].
  • Importantly, Nf1-/- spinal cord-derived oligodendrocyte progenitors, which are amplified 12-fold, retain the ability to form oligodendrocytes after in vivo transplantation [32].
  • However, FK228 is still in clinical trials (phase 2) for a variety of cancers (but not for NF as yet), and not available for most cancer/NF patients [39].
  • Recent clinical data suggest that NF1 might be also associated with an increased risk of t-AML after treatment with alkyating agents [27].
  • Immunocytochemistry on sections of cortex and cerebellum of unaffected and NF1 individuals and wild-type and NF1-deficient mice showed that the distribution of neurofibromin was similar to that reported for rat [40].


  1. Nf1 has an essential role in endothelial cells. Gitler, A.D., Zhu, Y., Ismat, F.A., Lu, M.M., Yamauchi, Y., Parada, L.F., Epstein, J.A. Nat. Genet. (2003) [Pubmed]
  2. Mouse models of tumor development in neurofibromatosis type 1. Cichowski, K., Shih, T.S., Schmitt, E., Santiago, S., Reilly, K., McLaughlin, M.E., Bronson, R.T., Jacks, T. Science (1999) [Pubmed]
  3. Nf1 and Gmcsf interact in myeloid leukemogenesis. Birnbaum, R.A., O'Marcaigh, A., Wardak, Z., Zhang, Y.Y., Dranoff, G., Jacks, T., Clapp, D.W., Shannon, K.M. Mol. Cell (2000) [Pubmed]
  4. Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects. Reilly, K.M., Tuskan, R.G., Christy, E., Loisel, D.A., Ledger, J., Bronson, R.T., Smith, C.D., Tsang, S., Munroe, D.J., Jacks, T. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. Multiple roles for neurofibromin in skeletal development and growth. Kolanczyk, M., Kossler, N., Kühnisch, J., Lavitas, L., Stricker, S., Wilkening, U., Manjubala, I., Fratzl, P., Spörle, R., Herrmann, B.G., Parada, L.F., Kornak, U., Mundlos, S. Hum. Mol. Genet. (2007) [Pubmed]
  6. Neurofibromatosis-1 (Nf1) heterozygous brain microglia elaborate paracrine factors that promote Nf1-deficient astrocyte and glioma growth. Daginakatte, G.C., Gutmann, D.H. Hum. Mol. Genet. (2007) [Pubmed]
  7. Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells. Wu, J., Williams, J.P., Rizvi, T.A., Kordich, J.J., Witte, D., Meijer, D., Stemmer-Rachamimov, A.O., Cancelas, J.A., Ratner, N. Cancer. Cell (2008) [Pubmed]
  8. The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells. Joseph, N.M., Mosher, J.T., Buchstaller, J., Snider, P., McKeever, P.E., Lim, M., Conway, S.J., Parada, L.F., Zhu, Y., Morrison, S.J. Cancer. Cell (2008) [Pubmed]
  9. The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Li, W., Cui, Y., Kushner, S.A., Brown, R.A., Jentsch, J.D., Frankland, P.W., Cannon, T.D., Silva, A.J. Curr. Biol. (2005) [Pubmed]
  10. Neurofibromatosis type 1: pathology, clinical features and molecular genetics. von Deimling, A., Krone, W., Menon, A.G. Brain Pathol. (1995) [Pubmed]
  11. Neurocognitive dysfunction in children with neurofibromatosis type 1. Rosser, T.L., Packer, R.J. Current neurology and neuroscience reports. (2003) [Pubmed]
  12. Isolation of mouse neuritic mRNAs. Reis, S.A., Oostra, B.A., Willemsen, R. J. Mol. Histol. (2006) [Pubmed]
  13. Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology. Fernandez-Valle, C., Tang, Y., Ricard, J., Rodenas-Ruano, A., Taylor, A., Hackler, E., Biggerstaff, J., Iacovelli, J. Nat. Genet. (2002) [Pubmed]
  14. Learning deficits, but normal development and tumor predisposition, in mice lacking exon 23a of Nf1. Costa, R.M., Yang, T., Huynh, D.P., Pulst, S.M., Viskochil, D.H., Silva, A.J., Brannan, C.I. Nat. Genet. (2001) [Pubmed]
  15. Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Reilly, K.M., Loisel, D.A., Bronson, R.T., McLaughlin, M.E., Jacks, T. Nat. Genet. (2000) [Pubmed]
  16. A mouse model for the learning and memory deficits associated with neurofibromatosis type I. Silva, A.J., Frankland, P.W., Marowitz, Z., Friedman, E., Laszlo, G.S., Cioffi, D., Jacks, T., Bourtchuladze, R., Lazlo, G. Nat. Genet. (1997) [Pubmed]
  17. Schwannomin isoform-1 interacts with syntenin via PDZ domains. Jannatipour, M., Dion, P., Khan, S., Jindal, H., Fan, X., Laganière, J., Chishti, A.H., Rouleau, G.A. J. Biol. Chem. (2001) [Pubmed]
  18. Mice with GFAP-targeted loss of neurofibromin demonstrate increased axonal MET expression with aging. Su, W., Xing, R., Guha, A., Gutmann, D.H., Sherman, L.S. Glia (2007) [Pubmed]
  19. In vitro and in vivo effects of a farnesyltransferase inhibitor on Nf1-deficient hematopoietic cells. Mahgoub, N., Taylor, B.R., Gratiot, M., Kohl, N.E., Gibbs, J.B., Jacks, T., Shannon, K.M. Blood (1999) [Pubmed]
  20. Differential modulation of malignant peripheral nerve sheath tumor growth by omega-3 and omega-6 fatty acids. Mashour, G.A., Drissel, S.N., Frahm, S., Farassati, F., Martuza, R.L., Mautner, V.F., Kindler-Röhrborn, A., Kurtz, A. Oncogene (2005) [Pubmed]
  21. Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1. Costa, R.M., Silva, A.J. J. Child Neurol. (2002) [Pubmed]
  22. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Costa, R.M., Federov, N.B., Kogan, J.H., Murphy, G.G., Stern, J., Ohno, M., Kucherlapati, R., Jacks, T., Silva, A.J. Nature (2002) [Pubmed]
  23. Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo. Ingram, D.A., Yang, F.C., Travers, J.B., Wenning, M.J., Hiatt, K., New, S., Hood, A., Shannon, K., Williams, D.A., Clapp, D.W. J. Exp. Med. (2000) [Pubmed]
  24. Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells. Yang, F.C., Ingram, D.A., Chen, S., Hingtgen, C.M., Ratner, N., Monk, K.R., Clegg, T., White, H., Mead, L., Wenning, M.J., Williams, D.A., Kapur, R., Atkinson, S.J., Clapp, D.W. J. Clin. Invest. (2003) [Pubmed]
  25. Loss of the nf1 tumor suppressor gene decreases fas antigen expression in myeloid cells. Hiatt, K., Ingram, D.A., Huddleston, H., Spandau, D.F., Kapur, R., Clapp, D.W. Am. J. Pathol. (2004) [Pubmed]
  26. The interferon consensus sequence-binding protein activates transcription of the gene encoding neurofibromin 1. Zhu, C., Saberwal, G., Lu, Y., Platanias, L.C., Eklund, E.A. J. Biol. Chem. (2004) [Pubmed]
  27. Myeloid malignancies induced by alkylating agents in Nf1 mice. Mahgoub, N., Taylor, B.R., Le Beau, M.M., Gratiot, M., Carlson, K.M., Atwater, S.K., Jacks, T., Shannon, K.M. Blood (1999) [Pubmed]
  28. Neurofibromatosis type 1 gene haploinsufficiency reduces AP-1 gene expression without abrogating the anabolic effect of parathyroid hormone. Yu, X., Milas, J., Watanabe, N., Rao, N., Murthy, S., Potter, O.L., Wenning, M.J., Clapp, W.D., Hock, J.M. Calcif. Tissue Int. (2006) [Pubmed]
  29. The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation. McClatchey, A.I., Saotome, I., Ramesh, V., Gusella, J.F., Jacks, T. Genes Dev. (1997) [Pubmed]
  30. A novel isoform of beta-spectrin II localizes to cerebellar Purkinje-cell bodies and interacts with neurofibromatosis type 2 gene product schwannomin. Chen, Y., Yu, P., Lu, D., Tagle, D.A., Cai, T. J. Mol. Neurosci. (2001) [Pubmed]
  31. Role of TC21/R-Ras2 in enhanced migration of neurofibromin-deficient Schwann cells. Huang, Y., Rangwala, F., Fulkerson, P.C., Ling, B., Reed, E., Cox, A.D., Kamholz, J., Ratner, N. Oncogene (2004) [Pubmed]
  32. Aberrant growth and differentiation of oligodendrocyte progenitors in neurofibromatosis type 1 mutants. Bennett, M.R., Rizvi, T.A., Karyala, S., McKinnon, R.D., Ratner, N. J. Neurosci. (2003) [Pubmed]
  33. Regulation of the Neurofibromatosis 2 gene promoter expression during embryonic development. Akhmametyeva, E.M., Mihaylova, M.M., Luo, H., Kharzai, S., Welling, D.B., Chang, L.S. Dev. Dyn. (2006) [Pubmed]
  34. Hyperactivation of p21(ras) and the hematopoietic-specific Rho GTPase, Rac2, cooperate to alter the proliferation of neurofibromin-deficient mast cells in vivo and in vitro. Ingram, D.A., Hiatt, K., King, A.J., Fisher, L., Shivakumar, R., Derstine, C., Wenning, M.J., Diaz, B., Travers, J.B., Hood, A., Marshall, M., Williams, D.A., Clapp, D.W. J. Exp. Med. (2001) [Pubmed]
  35. Neurofibromin deficiency in mice causes exencephaly and is a modifier for Splotch neural tube defects. Lakkis, M.M., Golden, J.A., O'Shea, K.S., Epstein, J.A. Dev. Biol. (1999) [Pubmed]
  36. Restored plasticity in a mouse model of neurofibromatosis type 1 via inhibition of hyperactive ERK and CREB. Guilding, C., McNair, K., Stone, T.W., Morris, B.J. Eur. J. Neurosci. (2007) [Pubmed]
  37. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. McClatchey, A.I., Saotome, I., Mercer, K., Crowley, D., Gusella, J.F., Bronson, R.T., Jacks, T. Genes Dev. (1998) [Pubmed]
  38. Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. Brannan, C.I., Perkins, A.S., Vogel, K.S., Ratner, N., Nordlund, M.L., Reid, S.W., Buchberg, A.M., Jenkins, N.A., Parada, L.F., Copeland, N.G. Genes Dev. (1994) [Pubmed]
  39. Sichuan pepper extracts block the PAK1/cyclin D1 pathway and the growth of NF1-deficient cancer xenograft in mice. Hirokawa, Y., Nheu, T., Grimm, K., Mautner, V., Maeda, S., Yoshida, M., Komiyama, K., Maruta, H. Cancer Biol. Ther. (2006) [Pubmed]
  40. Neurofibromin expression and astrogliosis in neurofibromatosis (type 1) brains. Nordlund, M.L., Rizvi, T.A., Brannan, C.I., Ratner, N. J. Neuropathol. Exp. Neurol. (1995) [Pubmed]
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