JAX Mouse Strain Datasheet - 008191

B6;129S2-Trp53^tm1Tyj Nf1^tm1Tyj/J

Stock No:: 008191

Targeted Mutation

Cryo Recovery

Overview

These mice carry Trp53 and Nf1 targeted mutations on the same homolog of chromosome 11 (in cis). These mutations are approximately 10 Mbp apart and may segregate independently of one another. Double heterozygotes survive an average of five months and exhibit a significant increase in the percentage of soft tissue sarcomas. About 30% of tumors from the Nf1/Trp53 cis animals stain positively for S100 (consistent with glial cell origin) and exhibit classic histological features of malignant peripheral nerve sheath tumors (MPNSTs). This strain may be useful in studies of astrocytomas/glioblastomas and tumor suppressor genes.

Donating Investigator

Dr. Tyler Jacks, Massachusetts Institute of Technology

Genetic overview

Genetic Background	Generation

Nf1^tm1Tyj

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Nf1	neurofibromin 1

Trp53^tm1Tyj

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Trp53	transformation related protein 53

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Research Applications

Cancer Research
Developmental Biology Research
Apoptosis Research
Immunology, Inflammation and Autoimmunity Research
Research Tools

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Base Price

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$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

These mice carry Trp53 and Nf1 targeted mutations (in cis) on chromosome 11. These mutations are approximately 10 Mbp apart and may segregate independently of one another. Double homozygotes are embryonic lethal. Double heterozygotes survive an average of five months and exhibit a significant increase in the percentage of soft tissue sarcomas compared with mice of other genotypes (Nf1 +/-, 5%; p53, 57%; Nf1/Trp53 trans, 36%; Nf1/Trp53 cis, 81%). Furthermore, although Nf1/Trp53 trans mice exclusively develop osteo-, fibro-, rhabdomyo-, and hemangiosarcomas, about 30% of tumors from the Nf1/Trp53 cis animals stain positively for S100 (consistent with glial cell origin) and exhibit classic histological features of malignant peripheral nerve sheath tumors (MPNSTs). This strain may be useful in studies of astrocytomas/glioblastomas and tumor suppressor genes.

Development

These mice carry two independently-created targeted mutations, Trp53^tm1Tjy and Nf1^tm1Tyj, that are approximately 10 Mbp apart on the same homolog of chromosome 11 (in cis). To create the Trp53 mutation, a targeting vector was designed to replace approximately 40% of the coding sequences (involving exons 2-6) with a neomycin resistance cassette. To create the Nf1 mutation, a targeting vector was designed to insert a neomycin resistance cassette and delete the first 42 codons of exon 31, the exon 31 splice acceptor site, and approximately 2 kb of intron 30. Each of the targeting vectors was independently electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Independent strains carrying germline mutations in Trp53 and Nf1 were generated on a mixed 129S2/SvPas and C57BL/6 genetic background, and then then intercrossed. Mice that underwent meiotic recombination events placing both mutations on the same homolog of chromosome 11 (in cis) were selected. This double mutant strain was maintained on a mixed 129S2/SvPas and C57BL/6 genetic background by the donating laboratory prior to sending to The Jackson Laboratory Repository. Upon arrival, males that were heterozygous for both mutations were identified and used to cryopreserve sperm.

Selected References

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: J:64364

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Genetics

Nf1^tm1Tyj

Allele Symbol: Nf1^tm1Tyj

Allele Name	targeted mutation 1, Tyler Jacks
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Nf1-; Nf1ⁿ³¹
Gene Symbol and Name	Nf1, neurofibromin 1
Gene Synonym(s)	AW494271; Dsk9; Dsk9; Martin Hrabe de Angelis dark skin 9; Mhdadsk9; Mhdadsk9; NFNS; Nf-1; Nf-1; VRNF; WSS; dark skin 9; expressed sequence AW494271; neurofibromatosis 1; neurofibromin
Site of Expression	Nf1 is normally widely expressed.
Strain of Origin	129S2/SvPas
Chromosome	11
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.
Mutations Made By	Dr. Tyler Jacks, Massachusetts Institute of Technology

Trp53^tm1Tyj

Allele Symbol: Trp53^tm1Tyj

Allele Name	targeted mutation 1, Tyler Jacks
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Trp53-; Trp53^KO; p53-; p53^delta; p53^null; p53KO
Gene Symbol and Name	Trp53, transformation related protein 53
Gene Synonym(s)	BCC7; LFS1; P53; TRP53; p44; p53
Site of Expression	Normal Trp53 expression is widespread.
Strain of Origin	129S2/SvPas
Chromosome	11
General Note	This mutant allele was produced by a targeted neo insertion into the Trp53 locus. Homozygotes show no visible phenotype but develop tumors at 3-6 months of age. Heterozygotes develop tumors at 10 months of age. These mice model some of the features of human Li-Fraumeni syndrome (OMIM 151623), a form of familial breast cancer with mutations in TRP53 (J:16022)(J:16023) A specific human mutation found in hepatocellular carcinomas caused by hepatitis B infection or by aflatoxin exposure has been created in a mouse model, resulting in a similar gene product (J:27363).
Molecular Note	A neomycin cassette replaced 40% of the coding sequences beginning with exon 2 (upstream of the translation start site) and extending into exon 6.
Mutations Made By	Dr. Tyler Jacks, Massachusetts Institute of Technology

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Cancer Research
- Increased Tumor Incidence
  - Other Tissues/Organs
  - Other Tissues/Organs: brain
- Tumor Suppressor Genes
Developmental Biology Research
- Embryonic Lethality (Homozygous)

Genotype: Trp53^tm1Tyj related

Apoptosis Research
- Endogenous Regulators
Cancer Research
- Increased Tumor Incidence
  - Lymphomas
  - Other Tissues/Organs
  - Other Tissues/Organs: osteosarcoma
- Toxicology
- Tumor Suppressor Genes
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules
Research Tools
- Toxicology Research
  - B and T cell deficiency, xenograft transplant host
  - drug/compound testing

Mammalian Phenotype Terms by Genotype

Genotype: Nf1^tm1Tyj/Nf1⁺ Trp53^tm1Tyj/Trp53⁺
involves: 129/Sv * C57BL/6

nervous system phenotype

increased neurofibrosarcoma incidence
- develop in cis-double heterozygotes, usually correlated with loss of one chromosome

mortality/aging

premature death
- cis-double heterozygotes die by 5 months of age and trans-double heterozygotes survive to the average age of 10 months

neoplasm

increased neurofibrosarcoma incidence
- develop in cis-double heterozygotes, usually correlated with loss of one chromosome

increased sarcoma incidence
- developed in both cis- and trans-double heterozygotes
- sarcomas in trans-double heterozygotes were similar to those found in mice with either single mutation and were usually correlated with loss of one chromosome

increased tumor incidence
- cis-double heterozygotes exhibit greater incidence of tumors than trans-double heterozygotes

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Nf1^tm1Tyj/Nf1⁺ Trp53^tm1Tyj/Trp53⁺
involves: 129S2/SvPas

nervous system phenotype

increased neurofibrosarcoma incidence
- form by 6 months of age

nervous system phenotype
- neural crest stem cells do not abnormally persist in the peripheral nervous system in adult mice

neoplasm

increased neurofibrosarcoma incidence
- form by 6 months of age

References

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: J:64364

Additional - 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: J:186764
Bessler WK; Kim G; Hudson FZ; Mund JA; Mali R; Menon K; Kapur R; Clapp DW; Ingram DA Jr; Stansfield BK. 2016. Nf1+/- monocytes/macrophages induce neointima formation via CCR2 activation. Hum Mol Genet 25(6):1129-39. PubMed: 26740548 MGI: J:229474
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: 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: 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: 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: 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: 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: J:167633
Choi G; Huang B; Pinarbasi E; Braunstein SE; Horvai AE; Kogan S; Bhatia S; Faddegon B; Nakamura JL. 2012. Genetically mediated Nf1 loss in mice promotes diverse radiation-induced tumors modeling second malignant neoplasms. Cancer Res 72(24):6425-34. PubMed: 23071067 MGI: J:193638
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: 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: 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: J:191670
De Raedt T; Beert E; Pasmant E; Luscan A; Brems H; Ortonne N; Helin K; Hornick JL; Mautner V; Kehrer-Sawatzki H; Clapp W; Bradner J; Vidaud M; Upadhyaya M; Legius E; Cichowski K. 2014. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature 514(7521):247-51. PubMed: 25119042 MGI: J:217077
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: J:175966
Deo M; Huang JL; Fuchs H; de Angelis MH; Van Raamsdonk CD. 2013. Differential effects of neurofibromin gene dosage on melanocyte development. J Invest Dermatol 133(1):49-58. PubMed: 22810304 MGI: J:196495
Duan JH; Hodgdon KE; Hingtgen CM; Nicol GD. 2014. N-type calcium current, Cav2.2, is enhanced in small-diameter sensory neurons isolated from Nf1+/- mice. Neuroscience 270:192-202. PubMed: 24755485 MGI: J:210619
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: J:79702
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: J:18542
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: 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: 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: 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: 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: 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: 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: 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: J:158570
Lepoutre-Lussey C; Thibault C; Buffet A; Morin A; Badoual C; Benit P; Rustin P; Ottolenghi C; Janin M; Castro-Vega LJ; Trapman J; Gimenez-Roqueplo AP; Favier J. 2016. From Nf1 to Sdhb knockout: Successes and failures in the quest for animal models of pheochromocytoma. Mol Cell Endocrinol 421:40-8. PubMed: 26123588 MGI: J:236514
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: 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: J:103691
Lock R; Ingraham R; Maertens O; Miller AL; Weledji N; Legius E; Konicek BM; Yan SC; Graff JR; Cichowski K. 2016. Cotargeting MNK and MEK kinases induces the regression of NF1-mutant cancers. J Clin Invest 126(6):2181-90. PubMed: 27159396 MGI: J:237073
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: 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: J:55413
Malone CF; Fromm JA; Maertens O; DeRaedt T; Ingraham R; Cichowski K. 2014. Defining key signaling nodes and therapeutic biomarkers in NF1-mutant cancers. Cancer Discov 4(9):1062-73. PubMed: 24913553 MGI: J:217840
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: 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: J:142439
Molosh AI; Johnson PL; Spence JP; Arendt D; Federici LM; Bernabe C; Janasik SP; Segu ZM; Khanna R; Goswami C; Zhu W; Park SJ; Li L; Mechref YS; Clapp DW; Shekhar A. 2014. Social learning and amygdala disruptions in Nf1 mice are rescued by blocking p21-activated kinase. Nat Neurosci 17(11):1583-90. PubMed: 25242307 MGI: J:219424
Mroue R; Huang B; Braunstein S; Firestone AJ; Nakamura JL. 2015. Monoallelic loss of the imprinted gene Grb10 promotes tumor formation in irradiated Nf1+/- mice. PLoS Genet 11(5):e1005235. PubMed: 26000738 MGI: J:224780
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: 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: 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: 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: 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: 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: 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: J:105038
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: J:92444
Rhodes SD; Wu X; He Y; Chen S; Yang H; Staser KW; Wang J; Zhang P; Jiang C; Yokota H; Dong R; Peng X; Yang X; Murthy S; Azhar M; Mohammad KS; Xu M; Guise TA; Yang FC. 2013. Hyperactive transforming growth factor-beta1 signaling potentiates skeletal defects in a neurofibromatosis type 1 mouse model. J Bone Miner Res 28(12):2476-89. PubMed: 23703870 MGI: J:231256
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Ribeiro S; Napoli I; White IJ; Parrinello S; Flanagan AM; Suter U; Parada LF; Lloyd AC. 2013. Injury signals cooperate with Nf1 loss to relieve the tumor-suppressive environment of adult peripheral nerve. Cell Rep 5(1):126-36. PubMed: 24075988 MGI: J:203786
Sanchez-Macedo N; Feng J; Faubert B; Chang N; Elia A; Rushing EJ; Tsuchihara K; Bungard D; Berger SL; Jones RG; Mak TW; Zaugg K. 2013. Depletion of the novel p53-target gene carnitine palmitoyltransferase 1C delays tumor growth in the neurofibromatosis type I tumor model. Cell Death Differ 20(4):659-68. PubMed: 23412344 MGI: J:228258
Sharma R; Wu X; Rhodes SD; Chen S; He Y; Yuan J; Li J; Yang X; Li X; Jiang L; Kim ET; Stevenson DA; Viskochil D; Xu M; Yang FC. 2013. Hyperactive Ras/MAPK signaling is critical for tibial nonunion fracture in neurofibromin-deficient mice. Hum Mol Genet 22(23):4818-28. PubMed: 23863460 MGI: J:202235
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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: J:192569
Stansfield BK; Bessler WK; Mali R; Mund JA; Downing BD; Kapur R; Ingram DA Jr. 2014. Ras-Mek-Erk signaling regulates Nf1 heterozygous neointima formation. Am J Pathol 184(1):79-85. PubMed: 24211110 MGI: J:205128
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Zhang L; Anglesio MS; O'sullivan M; Zhang F; Yang G; Sarao R; Nghiem MP; Cronin S; Hara H; Melnyk N; Li L; Wada T; Liu PP; Farrar J; Arceci RJ; Sorensen PH; Penninger JM. 2007. The E3 ligase HACE1 is a critical chromosome 6q21 tumor suppressor involved in multiple cancers. Nat Med 13(9):1060-1069. PubMed: 17694067 MGI: J:125183
Zhang L; Reynolds TL; Shan X; Desiderio S. 2011. Coupling of v(d)j recombination to the cell cycle suppresses genomic instability and lymphoid tumorigenesis. Immunity 34(2):163-74. PubMed: 21349429 MGI: J:168974
Zhang M; Behbod F; Atkinson RL; Landis MD; Kittrell F; Edwards D; Medina D; Tsimelzon A; Hilsenbeck S; Green JE; Michalowska AM; Rosen JM. 2008. Identification of tumor-initiating cells in a p53-null mouse model of breast cancer. Cancer Res 68(12):4674-82. PubMed: 18559513 MGI: J:138898
Zhang Q; He X; Chen L; Zhang C; Gao X; Yang Z; Liu G. 2012. Synergistic regulation of p53 by Mdm2 and Mdm4 is critical in cardiac endocardial cushion morphogenesis during heart development. J Pathol 228(3):416-28. PubMed: 22821713 MGI: J:188490
Zhang S; Zheng M; Kibe R; Huang Y; Marrero L; Warren S; Zieske AW; Iwakuma T; Kolls JK; Cui Y. 2011. Trp53 negatively regulates autoimmunity via the STAT3-Th17 axis. FASEB J 25(7):2387-98. PubMed: 21471252 MGI: J:174321
Zhang X; Podsypanina K; Huang S; Mohsin SK; Chamness GC; Hatsell S; Cowin P; Schiff R; Li Y. 2005. Estrogen receptor positivity in mammary tumors of Wnt-1 transgenic mice is influenced by collaborating oncogenic mutations. Oncogene 24(26):4220-31. PubMed: 15824740 MGI: J:99546
Zhao F; Obermann S; von Wasielewski R; Haile L; Manns MP; Korangy F; Greten TF. 2009. Increase in frequency of myeloid-derived suppressor cells in mice with spontaneous pancreatic carcinoma. Immunology 128(1):141-9. PubMed: 19689743 MGI: J:162293
Zheng S; El-Naggar AK; Kim ES; Kurie JM; Lozano G. 2007. A genetic mouse model for metastatic lung cancer with gender differences in survival. Oncogene 26(48):6896-904. PubMed: 17486075 MGI: J:129627
Zhou S; Gu L; He J; Zhang H; Zhou M. 2011. MDM2 Regulates Vascular Endothelial Growth Factor mRNA Stabilization in Hypoxia. Mol Cell Biol 31(24):4928-37. PubMed: 21986500 MGI: J:178311
Zhu F; Dolle ME; Berton TR; Kuiper RV; Capps C; Espejo A; McArthur MJ; Bedford MT; van Steeg H; de Vries A; Johnson DG. 2010. Mouse models for the p53 R72P polymorphism mimic human phenotypes. Cancer Res 70(14):5851-9. PubMed: 20587514 MGI: J:162466
Zhu M; Weiss RS. 2007. Increased common fragile site expression, cell proliferation defects, and apoptosis following conditional inactivation of mouse Hus1 in primary cultured cells. Mol Biol Cell 18(3):1044-55. PubMed: 17215515 MGI: J:123894
Zhu Y; Guignard F; Zhao D; Liu L; Burns DK; Mason RP; Messing A; Parada LF. 2005. Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell 8(2):119-30. PubMed: 16098465 MGI: J:101868
Zhuang J; Kamp WM; Li J; Liu C; Kang JG; Wang PY; Hwang PM. 2016. Forkhead Box O3A (FOXO3) and the Mitochondrial Disulfide Relay Carrier (CHCHD4) Regulate p53 Protein Nuclear Activity in Response to Exercise. J Biol Chem 291(48):24819-24827. PubMed: 27687729 MGI: J:237639
Zhuang J; Wang PY; Huang X; Chen X; Kang JG; Hwang PM. 2013. Mitochondrial disulfide relay mediates translocation of p53 and partitions its subcellular activity. Proc Natl Acad Sci U S A 110(43):17356-61. PubMed: 24101517 MGI: J:201969
Zindy F; Lee Y; Kawauchi D; Ayrault O; Merzoug LB; Li Y; McKinnon PJ; Roussel MF. 2015. Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation. PLoS One 10(6):e0129642. PubMed: 26091048 MGI: J:237792
Zindy F; Nilsson LM; Nguyen L; Meunier C; Smeyne RJ; Rehg JE; Eberhart C; Sherr CJ; Roussel MF. 2003. Hemangiosarcomas, medulloblastomas, and other tumors in Ink4c/p53-null mice. Cancer Res 63(17):5420-7. PubMed: 14500377 MGI: J:85515
Zou X; Cong F; Coutts M; Cattoretti G; Goff SP; Calame K. 2000. p53 deficiency increases transformation by v-Abl and rescues the ability of a C-terminally truncated v-Abl mutant To induce pre-B lymphoma In vivo Mol Cell Biol 20(2):628-33. PubMed: 10611241 MGI: J:59574
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Genetic overview

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Detailed Description

Development

Selected References

Nf1tm1Tyj

Allele Symbol: Nf1tm1Tyj

Trp53tm1Tyj

Allele Symbol: Trp53tm1Tyj

Disease Terms

Research Areas By Genotype

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

Genotype: Trp53tm1Tyj related

Mammalian Phenotype Terms by Genotype

Genotype: Nf1tm1Tyj/Nf1+ Trp53tm1Tyj/Trp53+involves: 129/Sv * C57BL/6

nervous system phenotype

mortality/aging

neoplasm

Genotype: Nf1tm1Tyj/Nf1+ Trp53tm1Tyj/Trp53+involves: 129S2/SvPas

nervous system phenotype

neoplasm

References

Additional - Nf1tm1Tyj related

Additional - Trp53tm1Tyj related

Genotyping Protocols

Breeding Considerations

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

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

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Nf1^tm1Tyj

Allele Symbol: Nf1^tm1Tyj

Trp53^tm1Tyj

Allele Symbol: Trp53^tm1Tyj

Genotype: Trp53^tm1Tyj related

Genotype: Nf1^tm1Tyj/Nf1⁺ Trp53^tm1Tyj/Trp53⁺
involves: 129/Sv * C57BL/6

Genotype: Nf1^tm1Tyj/Nf1⁺ Trp53^tm1Tyj/Trp53⁺
involves: 129S2/SvPas

Additional - Nf1^tm1Tyj related

Additional - Trp53^tm1Tyj related