Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Dr. Tyler Jacks,   Massachusetts Institute of Technology

Description
Heterozygous animals do not exhibit the classical symptoms of Human neurofibromatosis type 1, but are highly predisposed to the formation of various tumor types, notably phaeochromocytoma, a tumor of the neural crest-derived adrenal medulla, and myeloid leukemia. Homozygosity leads to abnormal cardiac development and mid-gestational embryonic lethality. This strain may be useful in studies of cancer and developmental biology.

Development
A targeting vector was use to replace the first 42 codons of exon 31, the exon 31 splice acceptor site, and approximately 2 kb of intron 30 with a neomycin resistance cassette (oriented in an opposite transcriptional direction). The vector was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. This strain was backcrossed to C57BL/6 background more than twelve times by the donating laboratory.

Related Strains

Strains carrying   Nf1^tm1Tyj allele

008191

B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J

View Strains carrying   Nf1^tm1Tyj     (1 strain)

Strains carrying other alleles of Nf1

017640	B6.129(Cg)-Nf1tm1Par/J
007923	B6.129S1-Nf1tm1Cbr/J
002646	B6.129S6-Nf1tm1Fcr/J
017530	STOCK Iis2tm2(ACTB-tdTomato,-EGFP)Luo Trp53tm1Tyj Nf1tm1Par/J
017639	STOCK Nf1tm1Par/J

View Strains carrying other alleles of Nf1     (5 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Neurofibromatosis, Type I; NF1

- No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.

Neurofibromatosis, Type I; NF1

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Juvenile Myelomonocytic Leukemia; JMML   (NF1) Neurofibromatosis, Familial Spinal   (NF1) Neurofibromatosis-Noonan Syndrome; NFNS   (NF1) Watson Syndrome   (NF1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Nf1^tm1Tyj/Nf1⁺

        involves: 129S2/SvPas * C57BL/6

• tumorigenesis
• increased tumor incidence
  • 75% of mice develop tumors over 27 months, including lymphomas, leukemias, lung adenocarcinomas, hepatomas, fibrosarcomas, neurofibrosarcoma, and adrenal tumors   (MGI Ref ID J:18542)
  • mice develop similar types of tumors seen in patients with neurofibromatosis, but do not present any other classical features of the disease   (MGI Ref ID J:18542)
• • increased adrenal gland tumor incidence   (MGI Ref ID J:18542)
  • • pheochromocytoma   (MGI Ref ID J:18542)
  • increased fibrosarcoma incidence   (MGI Ref ID J:18542)
  • • increased neurofibrosarcoma incidence   (MGI Ref ID J:18542)
  • increased hepatoma incidence   (MGI Ref ID J:18542)
  • increased lymphoma incidence   (MGI Ref ID J:18542)
  • leukemia
    • some heterozygotes developed lymphoid leukemia and myeloid leukemia   (MGI Ref ID J:18542)
  • lung adenocarcinoma   (MGI Ref ID J:18542)

Nf1^tm1Tyj/Nf1⁺

        involves: 129S2/SvPas * C57BL/6J

• behavior/neurological phenotype
• abnormal spatial learning
  • impairment in Morris Water Maze that was overcome with extensive training, however normal long term memory in cued fear conditioning test and normal nociception   (MGI Ref ID J:38703)

Nf1^tm1Tyj/Nf1⁺

        involves: 129S2/SvPas

• immune system phenotype
• abnormal mast cell physiology
  • bone marrow derived mast cells have about a 25% faster proliferation rate than controls when cultured for three days with SCF   (MGI Ref ID J:142439)
  • these mast cells also have a two-thirds higher migration rate towards SCF in transwell assays than controls   (MGI Ref ID J:142439)
  • a similar higher migration rate to the skin is observed in vivo when SCF is administered   (MGI Ref ID J:142439)
• • increased mast cell degranulation
    • the percent of degranulating mast cells in SCF-treated skin is almost 4 times that of controls   (MGI Ref ID J:142439)

Nf1^tm1Tyj/Nf1^tm1Tyj

        involves: 129S2/SvPas * C57BL/6

• mortality/aging
• complete embryonic lethality during organogenesis
  • between E12.5 and E14   (MGI Ref ID J:18542)
• cardiovascular system phenotype
• abnormal myocardium layer morphology
  • myocardium, particularly of the ventricles, was lacy in appearance and thinner than normal   (MGI Ref ID J:18542)
• distended pericardium   (MGI Ref ID J:18542)
• double outlet right ventricle   (MGI Ref ID J:18542)
• homeostasis/metabolism phenotype
• hydrops fetalis
  • begin to exhibit edema at E12.5   (MGI Ref ID J:18542)
• integument phenotype
• pallor   (MGI Ref ID J:18542)

Nf1^tm1Tyj/Nf1^tm1Tyj

        involves: 129S2/SvPas

• nervous system phenotype
• abnormal neural crest cell morphology
  • a higher percentage of cells behave as neural crest stem cells (form multipotent neurospheres) in cultures made from the sympathetic chain, dorsal root ganglia, and sciatic nerve, but not the gut, of E13 homozygous embryos compared to littermate controls   (MGI Ref ID J:131914)
  • neurospheres are larger, proliferation is increased, and the capacity for self-renewal is increased in cultured neural crest stem cells from the sympathetic chain, dorsal root ganglia, and sciatic nerve of E13 homozygous embryos compared to littermate controls   (MGI Ref ID J:131914)
  • when stimulated to differentiate these neural crest stem cells produce more glia without any decrease in any of the other cell types (neurons, myofibroblasts) produced   (MGI Ref ID J:131914)
  • survival of these neural crest stem cells is improved under adverse culture conditions compared to cells from littermate controls   (MGI Ref ID J:131914)
• embryogenesis phenotype
• abnormal neural crest cell morphology
  • a higher percentage of cells behave as neural crest stem cells (form multipotent neurospheres) in cultures made from the sympathetic chain, dorsal root ganglia, and sciatic nerve, but not the gut, of E13 homozygous embryos compared to littermate controls   (MGI Ref ID J:131914)
  • neurospheres are larger, proliferation is increased, and the capacity for self-renewal is increased in cultured neural crest stem cells from the sympathetic chain, dorsal root ganglia, and sciatic nerve of E13 homozygous embryos compared to littermate controls   (MGI Ref ID J:131914)
  • when stimulated to differentiate these neural crest stem cells produce more glia without any decrease in any of the other cell types (neurons, myofibroblasts) produced   (MGI Ref ID J:131914)
  • survival of these neural crest stem cells is improved under adverse culture conditions compared to cells from littermate controls   (MGI Ref ID J:131914)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cancer Research
Increased Tumor Incidence
      Cell/Tissue Type
      Cell/Tissue Type: adrenal cortical tumors
      Leukemia
Tumor Suppressor Genes

Developmental Biology Research
Embryonic Lethality (Homozygous)
Internal/Organ Defects
      heart

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Nf1tm1Tyj
Allele Name		targeted mutation 1, Tyler Jacks
Allele Type		Targeted (knock-out)
Common Name(s)		Nf1-; Nf1n31;
Mutation Made By		Dr. Tyler Jacks,   Massachusetts Institute of Technology
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Nf1, neurofibromatosis 1
Chromosome		11
Gene Common Name(s)		AW494271; NFNS; Nf-1; VRNF; WSS; expressed sequence AW494271; neurofibromin;
General Note		Phenotypic Similarity to Human Syndrome: Astrocytoma (J:64364)
Molecular Note		A neomycin resistance cassette replaced the first 42 codons of exon 31, the exon 31 splice acceptor site, and approximately 2 kb of intron 30. This allele is a null allele; no stable full-length protein is made. [MGI Ref ID J:18542]

Genotyping

Genotyping Information

Genotyping Protocols

Nf1^tm1Tyj, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Jacks T; Shih TS; Schmitt EM; Bronson RT; Bernards A; Weinberg RA. 1994. Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nat Genet 7(3):353-61. [PubMed: 7920653]  [MGI Ref ID J:18542]

Additional References

Nf1^tm1Tyj related

Amlin-Van Schaick JC; Kim S; DiFabio C; Lee MH; Broman KW; Reilly KM. 2012. Arlm1 is a male-specific modifier of astrocytoma resistance on mouse Chr 12. Neuro Oncol 14(2):160-74. [PubMed: 22234937]  [MGI Ref ID J:186764]

Birnbaum RA; O'Marcaigh A; Wardak Z; Zhang YY; Dranoff G; Jacks T; Clapp DW; Shannon KM. 2000. Nf1 and Gmcsf interact in myeloid leukemogenesis. Mol Cell 5(1):189-95. [PubMed: 10678181]  [MGI Ref ID J:60155]

Boyanapalli M; Lahoud OB; Messiaen L; Kim B; Anderle de Sylor MS; Duckett SJ; Somara S; Mikol DD. 2006. Neurofibromin binds to caveolin-1 and regulates ras, FAK, and Akt. Biochem Biophys Res Commun 340(4):1200-8. [PubMed: 16405917]  [MGI Ref ID J:104986]

Buchstaller J; McKeever PE; Morrison SJ. 2012. Tumorigenic Cells Are Common in Mouse MPNSTs but Their Frequency Depends upon Tumor Genotype and Assay Conditions. Cancer Cell 21(2):240-52. [PubMed: 22340596]  [MGI Ref ID J:181460]

Carbe C; Zhang X. 2011. Lens induction requires attenuation of ERK signaling by Nf1. Hum Mol Genet 20(7):1315-23. [PubMed: 21233129]  [MGI Ref ID J:169235]

Chao RC; Pyzel U; Fridlyand J; Kuo YM; Teel L; Haaga J; Borowsky A; Horvai A; Kogan SC; Bonifas J; Huey B; Jacks TE; Albertson DG; Shannon KM. 2005. Therapy-induced malignant neoplasms in Nf1 mutant mice. Cancer Cell 8(4):337-48. [PubMed: 16226708]  [MGI Ref ID J:103509]

Chen S; Burgin S; McDaniel A; Li X; Yuan J; Chen M; Khalaf W; Clapp DW; Yang FC. 2010. Nf1-/- Schwann cell-conditioned medium modulates mast cell degranulation by c-Kit-mediated hyperactivation of phosphatidylinositol 3-kinase. Am J Pathol 177(6):3125-32. [PubMed: 21037083]  [MGI Ref ID J:167633]

Cichowski K; Shih TS; Schmitt E; Santiago S; Reilly K; McLaughlin ME; Bronson RT; Jacks T. 1999. Mouse models of tumor development in neurofibromatosis type 1. Science 286(5447):2172-6. [PubMed: 10591652]  [MGI Ref ID J:58876]

Costa RM; Federov NB; Kogan JH; Murphy GG; Stern J; Ohno M; Kucherlapati R; Jacks T; Silva AJ. 2002. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 415(6871):526-30. [PubMed: 11793011]  [MGI Ref ID J:74257]

Dai C; Santagata S; Tang Z; Shi J; Cao J; Kwon H; Bronson RT; Whitesell L; Lindquist S. 2012. Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesis. J Clin Invest 122(10):3742-54. [PubMed: 22945628]  [MGI Ref ID J:191670]

De Raedt T; Walton Z; Yecies JL; Li D; Chen Y; Malone CF; Maertens O; Jeong SM; Bronson RT; Lebleu V; Kalluri R; Normant E; Haigis MC; Manning BD; Wong KK; Macleod KF; Cichowski K. 2011. Exploiting cancer cell vulnerabilities to develop a combination therapy for ras-driven tumors. Cancer Cell 20(3):400-13. [PubMed: 21907929]  [MGI Ref ID J:175966]

Gutmann DH; Winkeler E; Kabbarah O; Hedrick N; Dudley S; Goodfellow PJ; Liskay RM. 2003. Mlh1 deficiency accelerates myeloid leukemogenesis in neurofibromatosis 1 (Nf1) heterozygous mice. Oncogene 22(29):4581-5. [PubMed: 12881715]  [MGI Ref ID J:84658]

Hawes JJ; Tuskan RG; Reilly KM. 2007. Nf1 expression is dependent on strain background: implications for tumor suppressor haploinsufficiency studies. Neurogenetics 8(2):121-30. [PubMed: 17216419]  [MGI Ref ID J:121636]

He Y; Rhodes SD; Chen S; Wu X; Yuan J; Yang X; Jiang L; Li X; Takahashi N; Xu M; Mohammad KS; Guise TA; Yang FC. 2012. c-Fms signaling mediates neurofibromatosis Type-1 osteoclast gain-in-functions. PLoS One 7(11):e46900. [PubMed: 23144792]  [MGI Ref ID J:194861]

Henkemeyer M; Rossi DJ; Holmyard DP; Puri MC; Mbamalu G; Harpal K; Shih TS; Jacks T; Pawson T. 1995. Vascular system defects and neuronal apoptosis in mice lacking ras GTPase-activating protein. Nature 377(6551):695-701. [PubMed: 7477259]  [MGI Ref ID J:29825]

Hiatt K; Ingram DA; Huddleston H; Spandau DF; Kapur R; Clapp DW. 2004. Loss of the nf1 tumor suppressor gene decreases fas antigen expression in myeloid cells. Am J Pathol 164(4):1471-9. [PubMed: 15039234]  [MGI Ref ID J:89131]

Hingtgen CM; Roy SL; Clapp DW. 2006. Stimulus-evoked release of neuropeptides is enhanced in sensory neurons from mice with a heterozygous mutation of the Nf1 gene. Neuroscience 137(2):637-645. [PubMed: 16298082]  [MGI Ref ID J:104588]

Hodgdon KE; Hingtgen CM; Nicol GD. 2012. Dorsal root ganglia isolated from Nf1+/- mice exhibit increased levels of mRNA expression of voltage-dependent sodium channels. Neuroscience 206:237-44. [PubMed: 22260870]  [MGI Ref ID J:184640]

Huse JT; Holland EC. 2009. Genetically engineered mouse models of brain cancer and the promise of preclinical testing. Brain Pathol 19(1):132-43. [PubMed: 19076778]  [MGI Ref ID J:173443]

Ingram DA; Hiatt K; King AJ; Fisher L; Shivakumar R; Derstine C; Wenning MJ; Diaz B; Travers JB; Hood A; Marshall M; Williams DA; Clapp DW. 2001. 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. J Exp Med 194(1):57-69. [PubMed: 11435472]  [MGI Ref ID J:71331]

Ingram DA; Yang FC; Travers JB; Wenning MJ; Hiatt K; New S; Hood A; Shannon K; Williams DA; Clapp DW. 2000. Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo. J Exp Med 191(1):181-8. [PubMed: 10620616]  [MGI Ref ID J:59248]

Ingram DA; Zhang L; McCarthy J; Wenning MJ; Fisher L; Yang FC; Clapp DW; Kapur R. 2002. Lymphoproliferative defects in mice lacking the expression of neurofibromin: functional and biochemical consequences of Nf1 deficiency in T-cell development and function. Blood 100(10):3656-62. [PubMed: 12393709]  [MGI Ref ID J:79702]

Johannessen CM; Johnson BW; Williams SM; Chan AW; Reczek EE; Lynch RC; Rioth MJ; McClatchey A; Ryeom S; Cichowski K. 2008. TORC1 is essential for NF1-associated malignancies. Curr Biol 18(1):56-62. [PubMed: 18164202]  [MGI Ref ID J:144615]

Joseph NM; Mosher JT; Buchstaller J; Snider P; McKeever PE; Lim M; Conway SJ; Parada LF; Zhu Y; Morrison SJ. 2008. The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells. Cancer Cell 13(2):129-40. [PubMed: 18242513]  [MGI Ref ID J:131914]

Khalaf WF; Yang FC; Chen S; White H; Bessler W; Ingram DA; Clapp DW. 2007. K-ras is critical for modulating multiple c-kit-mediated cellular functions in wild-type and Nf1+/- mast cells. J Immunol 178(4):2527-34. [PubMed: 17277161]  [MGI Ref ID J:143972]

Koenigsmann J; Rudolph C; Sander S; Kershaw O; Gruber AD; Bullinger L; Schlegelberger B; Carstanjen D. 2009. Nf1 haploinsufficiency and Icsbp deficiency synergize in the development of leukemias. Blood 113(19):4690-701. [PubMed: 19228926]  [MGI Ref ID J:148716]

Lakkis MM; Epstein JA. 1998. Neurofibromin modulation of ras activity is required for normal endocardial-mesenchymal transformation in the developing heart. Development 125(22):4359-67. [PubMed: 9778496]  [MGI Ref ID J:50306]

Lakkis MM; Golden JA; O'Shea KS; Epstein JA. 1999. Neurofibromin deficiency in mice causes exencephaly and is a modifier for Splotch neural tube defects. Dev Biol 212(1):80-92. [PubMed: 10419687]  [MGI Ref ID J:56680]

Lasater EA; Bessler WK; Mead LE; Horn WE; Clapp DW; Conway SJ; Ingram DA; Li F. 2008. Nf1+/- mice have increased neointima formation via hyperactivation of a Gleevec sensitive molecular pathway. Hum Mol Genet 17(15):2336-44. [PubMed: 18442999]  [MGI Ref ID J:137662]

Lasater EA; Li F; Bessler WK; Estes ML; Vemula S; Hingtgen CM; Dinauer MC; Kapur R; Conway SJ; Ingram DA Jr. 2010. Genetic and cellular evidence of vascular inflammation in neurofibromin-deficient mice and humans. J Clin Invest 120(3):859-70. [PubMed: 20160346]  [MGI Ref ID J:158570]

Li F; Munchhof AM; White HA; Mead LE; Krier TR; Fenoglio A; Chen S; Wu X; Cai S; Yang FC; Ingram DA. 2006. Neurofibromin is a novel regulator of RAS-induced signals in primary vascular smooth muscle cells. Hum Mol Genet 15(11):1921-30. [PubMed: 16644864]  [MGI Ref ID J:109530]

Li W; Cui Y; Kushner SA; Brown RA; Jentsch JD; Frankland PW; Cannon TD; Silva AJ. 2005. The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Curr Biol 15(21):1961-7. [PubMed: 16271875]  [MGI Ref ID J:103691]

Mahgoub N; Taylor BR; Gratiot M; Kohl NE; Gibbs JB; Jacks T; Shannon KM. 1999. In vitro and in vivo effects of a farnesyltransferase inhibitor on Nf1-deficient hematopoietic cells. Blood 94(7):2469-76. [PubMed: 10498620]  [MGI Ref ID J:57842]

Mahgoub N; Taylor BR; Le Beau MM; Gratiot M; Carlson KM; Atwater SK ; Jacks T ; Shannon KM. 1999. Myeloid malignancies induced by alkylating agents in Nf1 mice. Blood 93(11):3617-23. [PubMed: 10339466]  [MGI Ref ID J:55413]

Mangues R; Corral T; Lu S; Symmans WF; Liu L; Pellicer A. 1998. NF1 inactivation cooperates with N-ras in in vivo lymphogenesis activating Erk by a mechanism independent of its Ras-GTPase accelerating activity. Oncogene 17(13):1705-16. [PubMed: 9796699]  [MGI Ref ID J:52704]

McDaniel AS; Allen JD; Park SJ; Jaffer ZM; Michels EG; Burgin SJ; Chen S; Bessler WK; Hofmann C; Ingram DA; Chernoff J; Clapp DW. 2008. Pak1 regulates multiple c-Kit mediated Ras-MAPK gain-in-function phenotypes in Nf1+/- mast cells. Blood 112(12):4646-54. [PubMed: 18768391]  [MGI Ref ID J:142439]

Munchhof AM; Li F; White HA; Mead LE; Krier TR; Fenoglio A; Li X; Yuan J; Yang FC; Ingram DA. 2006. Neurofibroma-associated growth factors activate a distinct signaling network to alter the function of neurofibromin-deficient endothelial cells. Hum Mol Genet 15(11):1858-69. [PubMed: 16648142]  [MGI Ref ID J:109532]

Nagasubramanian R; Hansen RJ; Delaney SM; Cherian MM; Samson LD; Kogan SC; Dolan ME. 2008. Survival and tumorigenesis in O6-methylguanine DNA methyltransferase-deficient mice following cyclophosphamide exposure. Mutagenesis 23(5):341-6. [PubMed: 18477655]  [MGI Ref ID J:152129]

Nakamura JL; Phong C; Pinarbasi E; Kogan SC; Vandenberg S; Horvai AE; Faddegon BA; Fiedler D; Shokat K; Houseman BT; Chao R; Pieper RO; Shannon K. 2011. Dose-dependent effects of focal fractionated irradiation on secondary malignant neoplasms in Nf1 mutant mice. Cancer Res 71(1):106-15. [PubMed: 21199799]  [MGI Ref ID J:167772]

Nebesio TD; Ming W; Chen S; Clegg T; Yuan J; Yang Y; Estwick SA; Li Y; Li X; Hingtgen CM; Yang FC. 2007. Neurofibromin-deficient Schwann cells have increased lysophosphatidic acid dependent survival and migration-implications for increased neurofibroma formation during pregnancy. Glia 55(5):527-36. [PubMed: 17236191]  [MGI Ref ID J:156102]

Patmore DM; Welch S; Fulkerson PC; Wu J; Choi K; Eaves D; Kordich JJ; Collins MH; Cripe TP; Ratner N. 2012. In vivo regulation of TGF-beta by R-Ras2 revealed through loss of the RasGAP protein NF1. Cancer Res 72(20):5317-27. [PubMed: 22918885]  [MGI Ref ID J:191804]

Pemov A; Park C; Reilly KM; Stewart DR. 2010. Evidence of perturbations of cell cycle and DNA repair pathways as a consequence of human and murine NF1-haploinsufficiency. BMC Genomics 11:194. [PubMed: 20307317]  [MGI Ref ID J:159679]

Reilly KM; Broman KW; Bronson RT; Tsang S; Loisel DA; Christy ES; Sun Z; Diehl J; Munroe DJ; Tuskan RG. 2006. An imprinted locus epistatically influences Nstr1 and Nstr2 to control resistance to nerve sheath tumors in a neurofibromatosis type 1 mouse model. Cancer Res 66(1):62-8. [PubMed: 16397217]  [MGI Ref ID J:105038]

Reilly KM; Loisel DA; Bronson RT; McLaughlin ME; Jacks T. 2000. Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects Nat Genet 26(1):109-13. [PubMed: 10973261]  [MGI Ref ID J:64364]

Reilly KM; Tuskan RG; Christy E; Loisel DA; Ledger J; Bronson RT; Smith CD; Tsang S; Munroe DJ; Jacks T. 2004. Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects. Proc Natl Acad Sci U S A 101(35):13008-13. [PubMed: 15319471]  [MGI Ref ID J:92444]

Silva AJ; Frankland PW; Marowitz Z; Friedman E; Lazlo G; Cioffi D; Jacks T; Bourtchuladze R. 1997. A mouse model for the learning and memory deficits associated with neurofibromatosis type I. Nat Genet 15(3):281-4. [PubMed: 9054942]  [MGI Ref ID J:38703]

Silvestre DC; Gil GA; Tomasini N; Bussolino DF; Caputto BL. 2010. Growth of peripheral and central nervous system tumors is supported by cytoplasmic c-Fos in humans and mice. PLoS One 5(3):e9544. [PubMed: 20209053]  [MGI Ref ID J:158701]

Stansfield BK; Bessler WK; Mali R; Mund JA; Downing B; Li F; Sarchet KN; Distasi MR; Conway SJ; Kapur R; Ingram DA Jr. 2013. Heterozygous inactivation of the Nf1 gene in myeloid cells enhances neointima formation via a rosuvastatin-sensitive cellular pathway. Hum Mol Genet 22(5):977-88. [PubMed: 23197650]  [MGI Ref ID J:192569]

Staser K; Yang FC; Clapp DW. 2010. Mast cells and the neurofibroma microenvironment. Blood 116(2):157-64. [PubMed: 20233971]  [MGI Ref ID J:162828]

Su W; Xing R; Guha A; Gutmann DH; Sherman LS. 2007. Mice with GFAP-targeted loss of neurofibromin demonstrate increased axonal MET expression with aging. Glia 55(7):723-33. [PubMed: 17348023]  [MGI Ref ID J:156097]

Vogel KS; Klesse LJ; Velasco-Miguel S; Meyers K; Rushing EJ; Parada LF. 1999. Mouse tumor model for neurofibromatosis type 1. Science 286(5447):2176-9. [PubMed: 10591653]  [MGI Ref ID J:58877]

Walrath JC; Fox K; Truffer E; Gregory Alvord W; Quinones OA; Reilly KM. 2009. Chr 19(A/J) modifies tumor resistance in a sex- and parent-of-origin-specific manner. Mamm Genome 20(4):214-23. [PubMed: 19347398]  [MGI Ref ID J:147432]

Wang HF; Shih YT; Chen CY; Chao HW; Lee MJ; Hsueh YP. 2011. Valosin-containing protein and neurofibromin interact to regulate dendritic spine density. J Clin Invest 121(12):4820-37. [PubMed: 22105171]  [MGI Ref ID J:184421]

Wang Y; Nicol GD; Clapp DW; Hingtgen CM. 2005. Sensory neurons from Nf1 haploinsufficient mice exhibit increased excitability. J Neurophysiol 94(6):3670-6. [PubMed: 16093333]  [MGI Ref ID J:128643]

Weiss WA; Aldape K; Mohapatra G; Feuerstein BG; Bishop JM. 1997. Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J 16(11):2985-95. [PubMed: 9214616]  [MGI Ref ID J:41126]

Weiss WA; Israel M; Cobbs C; Holland E; James CD; Louis DN; Marks C; McClatchey AI; Roberts T; Van Dyke T; Wetmore C; Chiu IM; Giovannini M; Guha A; Higgins RJ; Marino S; Radovanovic I; Reilly K; Aldape K. 2002. Neuropathology of genetically engineered mice: consensus report and recommendations from an international forum. Oncogene 21(49):7453-63. [PubMed: 12386807]  [MGI Ref ID J:79667]

Wu X; Estwick SA; Chen S; Yu M; Ming W; Nebesio TD; Li Y; Yuan J; Kapur R; Ingram D; Yoder MC; Yang FC. 2006. Neurofibromin plays a critical role in modulating osteoblast differentiation of mesenchymal stem/progenitor cells. Hum Mol Genet 15(19):2837-45. [PubMed: 16893911]  [MGI Ref ID J:114925]

Xu J; Ismat FA; Wang T; Yang J; Epstein JA. 2007. NF1 regulates a Ras-dependent vascular smooth muscle proliferative injury response. Circulation 116(19):2148-56. [PubMed: 17967772]  [MGI Ref ID J:142994]

Yan J; Chen S; Zhang Y; Li X; Li Y; Wu X; Yuan J; Robling AG; Karpur R; Chan RJ; Yang FC. 2008. Rac1 mediates the osteoclast gains-in-function induced by haploinsufficiency of Nf1. Hum Mol Genet 17(7):936-48. [PubMed: 18089636]  [MGI Ref ID J:132466]

Yang A; Reeves RH. 2011. Increased Survival following Tumorigenesis in Ts65Dn Mice That Model Down Syndrome. Cancer Res 71(10):3573-81. [PubMed: 21467166]  [MGI Ref ID J:171978]

Yang FC; Chen S; Clegg T; Li X; Morgan T; Estwick SA; Yuan J; Khalaf W; Burgin S; Travers J; Parada LF; Ingram DA; Clapp DW. 2006. Nf1+/- mast cells induce neurofibroma like phenotypes through secreted TGF-beta signaling. Hum Mol Genet 15(16):2421-37. [PubMed: 16835260]  [MGI Ref ID J:112050]

Yang FC; Chen S; Robling AG; Yu X; Nebesio TD; Yan J; Morgan T; Li X; Yuan J; Hock J; Ingram DA; Clapp DW. 2006. Hyperactivation of p21 and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functions. J Clin Invest 116(11):2880-91. [PubMed: 17053831]  [MGI Ref ID J:114609]

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Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, heterozygotes (prone to tumors) may be bred. Homozygotes are embryonic lethal.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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For Licensing and Use Restrictions view the link(s) below:
- Notice to customers in Canada.
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.