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Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S6 via EK.CCE ES cell line Donating Investigator Neal Copeland, National Institutes of Health Appearance
black
Related Genotype: a/aDescription
Mice homozygous for the Nf1tm1Fcr targeted mutation die during embryonic development due to severe heart malformation (~E13). They also show hyperplasia of neural crest-derived sympathetic ganglia. Heterozygotes do not exhibit any overt disease symptoms. However, as noted in a another targeted mutation deleting the same exon of the Nf1 gene (Jacks, et al., Nat Genetics 7:353-361, 1994), they do show a predisposition to many types of tumors and were recently shown to have deficits in learning and memory (Silva, et al., Nat Genetics 15:281-284, 1997).
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Nf1
007923 B6.129S1-Nf1tm1Cbr/J 008192 B6.129S2-Nf1tm1Tyj/J 008191 B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J View Strains carrying other alleles of Nf1 (3 strains)
Congenic Nomenclature
View Related Disease (OMIM) Terms
Related Disease (OMIM) Terms
Neurofibromatosis, Type I; NF1 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Nf1tm1Fcr/Nf1tm1Fcr
either: (involves: 129S/SvEv) or (involves: 129S/SvEv * C57BL/6J)
- lethality-prenatal/perinatal
- lethality throughout fetal growth and development (MGI Ref ID J:18048)
- die by E14.5
- cardiovascular system phenotype
- abnormal cardiac valve morphology (MGI Ref ID J:18048)
- cardiac valve abnormalities at E13.5
- abnormal mitral valve morphology (MGI Ref ID J:18048)
- leaflets of the mitral valve remain poorly condensed at E13.5
- abnormal heart development (MGI Ref ID J:18048)
- abnormal atrioventricular canal morphology (MGI Ref ID J:18048)
- at E13.5, the atrioventricular canal is composed of loosely arranged endothelial cells that lack the typical cellular density
- abnormal endocardial cushion morphology (MGI Ref ID J:18048)
- E13.5 endocardial cushion retains a loose, myxoid appearance that is seen at E12 in wild-type, even though it merges and divides the atrioventricular canal into the left and right channels
- increased endocardial cushion size (MGI Ref ID J:18048)
- considerably larger at E13.5
- persistent truncus arteriosis (MGI Ref ID J:18048)
- at E13.5, have a common root of the aorta and pulmonary artery departing from the conus cordis of the right ventricle
- as the truncus proceeds cephalad, it divides into two channels, the pulmonary artery and the aorta, which are not fully separate and are joined in a common external sheath
- abnormal heart shape (MGI Ref ID J:18048)
- globular heart
- abnormal vein morphology (MGI Ref ID J:18048)
- show distended veins
- abnormal ventricular septum morphology (MGI Ref ID J:18048)
- exhibit only a rudimentary septum near the apex that is exculsively muscular
- disorganized myocardium (MGI Ref ID J:18048)
- show disoriented and poorly developed myocardial fibers
- heart hypoplasia (MGI Ref ID J:18048)
- liver hemorrhage (MGI Ref ID J:18048)
- seen at E13.5
- pericardial effusion (MGI Ref ID J:18048)
- vasculature congestion (MGI Ref ID J:18048)
- liver/biliary system phenotype
- delayed hepatic development (MGI Ref ID J:18048)
- 18- to 24-hr delay in hepatic development
- focal hepatic necrosis (MGI Ref ID J:18048)
- seen at E13.5
- liver hypoplasia (MGI Ref ID J:18048)
- seen at E13.5
- pale liver (MGI Ref ID J:18048)
- muscle phenotype
- abnormal muscle morphology (MGI Ref ID J:18048)
- musculature of the stomach, the three layers of the abdominal musculature, and the muscles of the shoulder girdle are thinner
- abnormal skeletal muscle morphology (MGI Ref ID J:18048)
- skeletal muscle throughout the body is hypoplastic at E13.5
- delayed muscle development (MGI Ref ID J:18048)
- 18- to 24-hour delay in development of skeletal muscle
- disorganized myocardium (MGI Ref ID J:18048)
- show disoriented and poorly developed myocardial fibers
- renal/urinary system phenotype
- decreased renal glomerulus number (MGI Ref ID J:18048)
- reduced number of glomeruli at E13.5, due to developmental delay
- delayed kidney development (MGI Ref ID J:18048)
- 18- to 24-hr delay in renal development
- in the metanephros, display a retardation of cephalad repositioning at E13.5
- vision/eye phenotype
- microphthalmia (MGI Ref ID J:18048)
- nervous system phenotype
- exencephaly (MGI Ref ID J:18048)
- seen in about 6.3% of homozygotes
- paravertebral ganglia hyperplasia (MGI Ref ID J:18048)
- prevertebral ganglia hyperplasia (MGI Ref ID J:18048)
- growth/size phenotype
- enlarged chest (MGI Ref ID J:18048)
- display a chest bulge
- homeostasis/metabolism phenotype
- edema (MGI Ref ID J:18048)
- systemic edema
- immune system phenotype
- abnormal lymphatic vessel morphology (MGI Ref ID J:18048)
- show distended lymphatics
- respiratory system phenotype
- abnormal respiratory system morphology (MGI Ref ID J:18048)
- pleural effusion
- craniofacial phenotype
- megacephaly (MGI Ref ID J:18048)
Nf1tm1Fcr/Nf1tm1Fcr
involves: 129S/SvEvView Research Applications
Research Applications
This mouse can be used to support research in many areas including:Nf1tm1Fcr related
Cancer Research
Increased Tumor Incidence (Other Tissues/Organs: multiple)
Cardiovascular Research
Heart Abnormalities
Developmental Biology Research
Neurodevelopmental Defects
Internal/Organ Research
Heart Abnormalities
Mouse/Human Gene Homologs
Neurofibromatosis Type I
Neurobiology Research
Behavioral and Learning Defects
Neurodevelopmental Defects
| Allele Symbol | Nf1tm1Fcr | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Fredrick Cancer Research and Development Center | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Nf1-; Nf1Fcr; Nf1mut; | ||
| Mutation Made By | Camilynn Brannan, Univ of Florida College of Medicine | ||
| Strain of Origin | 129S/SvEv-Gpi1 | ||
| ES Cell Line Name | CCE/EK.CCE | ||
| ES Cell Line Strain | 129S/SvEv-Gpi1 | ||
| Gene Symbol and Name | Nf1, neurofibromatosis 1 | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | AW494271; DKFZp686J1293; FLJ21220; NFNS; Nf-1; VRNF; WSS; expressed sequence AW494271; neurofibromin; | ||
| Molecular Note | Insertion of a neomycin cassette in the opposite transcriptional orientation into exon 31 of the Nf1 gene. Exon 31 was chosen as the mutation site because several point mutations exist at this site in human NF1 patients. This allele is a null allele; no RNA or protein is made from this mutated allele. [MGI Ref ID J:18048] | ||
Genotyping Protocols
Nf1tm1Fcr, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Brannan CI; Perkins AS; Vogel KS; Ratner N; Nordlund ML; Reid SW; Buchberg AM; Jenkins NA; Parada LF; Copeland NG. 1994. Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues [published erratum appears in Genes Dev 1994 Nov 15;8(22):2792] Genes Dev 8(9):1019-29. [PubMed: 7926784] [MGI Ref ID J:18048]
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]
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]
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]
Nf1tm1Fcr relatedAtit RP; Crowe MJ; Greenhalgh DG; Wenstrup RJ; Ratner N. 1999. The Nf1 tumor suppressor regulates mouse skin wound healing, fibroblast proliferation, and collagen deposited by fibroblasts. J Invest Dermatol 112(6):835-42. [PubMed: 10383727] [MGI Ref ID J:55742]
Atit RP; Mitchell K; Nguyen L; Warshawsky D; Ratner N. 2000. The neurofibromatosis type 1 (Nf1) tumor suppressor is a modifier of carcinogen-induced pigmentation and papilloma formation in C57BL/6 mice. J Invest Dermatol 114(6):1093-100. [PubMed: 10844550] [MGI Ref ID J:62818]
Bajenaru ML; Donahoe J; Corral T; Reilly KM; Brophy S; Pellicer A; Gutmann DH. 2001. Neurofibromatosis 1 (NF1) heterozygosity results in a cell-autonomous growth advantage for astrocytes. Glia 33(4):314-23. [PubMed: 11246230] [MGI Ref ID J:80411]
Bajenaru ML; Garbow JR; Perry A; Hernandez MR; Gutmann DH. 2005. Natural history of neurofibromatosis 1-associated optic nerve glioma in mice. Ann Neurol 57(1):119-27. [PubMed: 15622533] [MGI Ref ID J:96293]
Bajenaru ML; Hernandez MR; Perry A; Zhu Y; Parada LF; Garbow JR; Gutmann DH. 2003. Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity. Cancer Res 63(24):8573-7. [PubMed: 14695164] [MGI Ref ID J:87063]
Bajenaru ML; Zhu Y; Hedrick NM; Donahoe J; Parada LF; Gutmann DH. 2002. Astrocyte-specific inactivation of the neurofibromatosis 1 gene (NF1) is insufficient for astrocytoma formation. Mol Cell Biol 22(14):5100-13. [PubMed: 12077339] [MGI Ref ID J:77208]
Banerjee D; Hegedus B; Gutmann DH; Garbow JR. 2007. Detection and measurement of neurofibromatosis-1 mouse optic glioma in vivo. Neuroimage 35(4):1434-7. [PubMed: 17383899] [MGI Ref ID J:122677]
Bennett MR; Rizvi TA; Karyala S; McKinnon RD; Ratner N. 2003. Aberrant growth and differentiation of oligodendrocyte progenitors in neurofibromatosis type 1 mutants. J Neurosci 23(18):7207-17. [PubMed: 12904481] [MGI Ref ID J:84861]
Dasgupta B; Gutmann DH. 2005. Neurofibromin regulates neural stem cell proliferation, survival, and astroglial differentiation in vitro and in vivo. J Neurosci 25(23):5584-94. [PubMed: 15944386] [MGI Ref ID J:98766]
Dasgupta B; Yi Y; Hegedus B; Weber JD; Gutmann DH. 2005. Cerebrospinal fluid proteomic analysis reveals dysregulation of methionine aminopeptidase-2 expression in human and mouse neurofibromatosis 1-associated glioma. Cancer Res 65(21):9843-50. [PubMed: 16267007] [MGI Ref ID J:102692]
Diwakar G; Zhang D; Jiang S; Hornyak TJ. 2008. Neurofibromin as a regulator of melanocyte development and differentiation. J Cell Sci 121(Pt 2):167-77. [PubMed: 18089649] [MGI Ref ID J:130856]
Garza R; Hudson RA rd; McMahan CA; Walter CA; Vogel KS. 2007. A mild mutator phenotype arises in a mouse model for malignancies associated with neurofibromatosis type 1. Mutat Res 615(1-2):98-110. [PubMed: 17208258] [MGI Ref ID J:117442]
Guilding C; McNair K; Stone TW; Morris BJ. 2007. Restored plasticity in a mouse model of neurofibromatosis type 1 via inhibition of hyperactive ERK and CREB. Eur J Neurosci 25(1):99-105. [PubMed: 17241271] [MGI Ref ID J:118619]
Gutmann DH; Loehr A; Zhang Y; Kim J; Henkemeyer M; Cashen A. 1999. Haploinsufficiency for the neurofibromatosis 1 (NF1) tumor suppressor results in increased astrocyte proliferation. Oncogene 18(31):4450-9. [PubMed: 10442636] [MGI Ref ID J:56902]
Ingram DA; Wenning MJ; Shannon K; Clapp DW. 2003. Leukemic potential of doubly mutant Nf1 and Wv hematopoietic cells. Blood 101(5):1984-6. [PubMed: 12393498] [MGI Ref ID J:82128]
Ismat FA; Xu J; Lu MM; Epstein JA. 2006. The neurofibromin GAP-related domain rescues endothelial but not neural crest development in Nf1 mice. J Clin Invest 116(9):2378-84. [PubMed: 16906226] [MGI Ref ID J:114455]
Kim A; Morgan K; Hasz DE; Wiesner SM; Lauchle JO; Geurts JL; Diers MD; Le DT; Kogan SC; Parada LF; Shannon K; Largaespada DA. 2007. Beta common receptor inactivation attenuates myeloproliferative disease in Nf1 mutant mice. Blood 109(4):1687-91. [PubMed: 17090653] [MGI Ref ID J:123850]
King D; Yang G; Thompson MA; Hiebert SW. 2002. Loss of neurofibromatosis-1 and p19(ARF) cooperate to induce a multiple tumor phenotype. Oncogene 21(32):4978-82. [PubMed: 12118376] [MGI Ref ID J:78079]
Klesse LJ; Parada LF. 1998. p21 ras and phosphatidylinositol-3 kinase are required for survival of wild-type and NF1 mutant sensory neurons. J Neurosci 18(24):10420-8. [PubMed: 9852579] [MGI Ref ID J:68953]
Largaespada DA; Brannan CI; Jenkins NA; Copeland NG. 1996. Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia. Nat Genet 12(2):137-43. [PubMed: 8563750] [MGI Ref ID J:31568]
Ling BC; Wu J; Miller SJ; Monk KR; Shamekh R; Rizvi TA; Decourten-Myers G; Vogel KS; DeClue JE; Ratner N. 2005. Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis. Cancer Cell 7(1):65-75. [PubMed: 15652750] [MGI Ref ID J:95933]
Mashour GA; Martuza RL; Kurtz A. 1999. Induction of melanogenic abnormalities in NF1+/- mutant mice by DMBA [letter] J Invest Dermatol 113(6):1133-4. [PubMed: 10594763] [MGI Ref ID J:59045]
Ozerdem U. 2004. Targeting neovascular pericytes in neurofibromatosis type 1. Angiogenesis 7(4):307-11. [PubMed: 15886874] [MGI Ref ID J:105408]
Rizvi TA; Akunuru S; de Courten-Myers G; Switzer RC 3rd; Nordlund ML ; Ratner N. 1999. Region-specific astrogliosis in brains of mice heterozygous for mutations in the neurofibromatosis type 1 (Nf1) tumor suppressor. Brain Res 816(1):111-23. [PubMed: 9878702] [MGI Ref ID J:51953]
Rizvi TA; Huang Y; Sidani A; Atit R; Largaespada DA; Boissy RE; Ratner N. 2002. A novel cytokine pathway suppresses glial cell melanogenesis after injury to adult nerve. J Neurosci 22(22):9831-40. [PubMed: 12427839] [MGI Ref ID J:109211]
Rosenbaum T; Engelbrecht V; Krolls W; van Dorsten FA; Hoehn-Berlage M; Lenard HG. 1999. MRI abnormalities in neurofibromatosis type 1 (NF1): a study of men and mice. Brain Dev 21(4):268-73. [PubMed: 10392751] [MGI Ref ID J:55949]
Sandsmark DK; Zhang H; Hegedus B; Pelletier CL; Weber JD; Gutmann DH. 2007. Nucleophosmin mediates mammalian target of rapamycin-dependent actin cytoskeleton dynamics and proliferation in neurofibromin-deficient astrocytes. Cancer Res 67(10):4790-9. [PubMed: 17510408] [MGI Ref ID J:121729]
Tong J; Hannan F; Zhu Y; Bernards A; Zhong Y. 2002. Neurofibromin regulates G protein-stimulated adenylyl cyclase activity. Nat Neurosci 5(2):95-6. [PubMed: 11788835] [MGI Ref ID J:109327]
Verchere CB; D'Alessio DA; Palmiter RD; Weir GC; Bonner-Weir S; Baskin DG; Kahn SE. 1996. Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide. Proc Natl Acad Sci U S A 93(8):3492-6. [PubMed: 8622964] [MGI Ref ID J:108871]
Vogel KS; Brannan CI; Jenkins NA; Copeland NG; Parada LF. 1995. Loss of neurofibromin results in neurotrophin-independent survival of embryonic sensory and sympathetic neurons. Cell 82(5):733-42. [PubMed: 7671302] [MGI Ref ID J:68952]
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]
Vogel KS; Parada LF. 1998. Sympathetic neuron survival and proliferation are prolonged by loss of p53 and neurofibromin. Mol Cell Neurosci 11(1-2):19-28. [PubMed: 9608530] [MGI Ref ID J:47680]
Warrington NM; Woerner BM; Daginakatte GC; Dasgupta B; Perry A; Gutmann DH; Rubin JB. 2007. Spatiotemporal Differences in CXCL12 Expression and Cyclic AMP Underlie the Unique Pattern of Optic Glioma Growth in Neurofibromatosis Type 1. Cancer Res 67(18):8588-95. [PubMed: 17875698] [MGI Ref ID J:124875]
Wehrle-Haller B; Meller M; Weston JA. 2001. Analysis of melanocyte precursors in Nf1 mutants reveals that MGF/KIT signaling promotes directed cell migration independent of its function in cell survival. Dev Biol 232(2):471-83. [PubMed: 11401406] [MGI Ref ID J:69377]
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 J; Crimmins JT; Monk KR; Williams JP; Fitzgerald ME; Tedesco S; Ratner N. 2006. Perinatal epidermal growth factor receptor blockade prevents peripheral nerve disruption in a mouse model reminiscent of benign world health organization grade I neurofibroma. Am J Pathol 168(5):1686-96. [PubMed: 16651634] [MGI Ref ID J:108591]
Wu M; Wallace MR; Muir D. 2006. Nf1 haploinsufficiency augments angiogenesis. Oncogene 25(16):2297-303. [PubMed: 16288202] [MGI Ref ID J:108781]
Xu Y; Chiamvimonvat N; Vazquez AE; Akunuru S; Ratner N; Yamoah EN. 2002. Gene-targeted deletion of neurofibromin enhances the expression of a transient outward K+ current in Schwann cells: a protein kinase A-mediated mechanism. J Neurosci 22(21):9194-202. [PubMed: 12417644] [MGI Ref ID J:123994]
Zhu Y; Ghosh P; Charnay P; Burns DK; Parada LF. 2002. Neurofibromas in NF1: Schwann cell origin and role of tumor environment. Science 296(5569):920-2. [PubMed: 11988578] [MGI Ref ID J:76359]
Zhu Y; Romero MI; Ghosh P; Ye Z; Charnay P; Rushing EJ; Marth JD; Parada LF. 2001. Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain. Genes Dev 15(7):859-76. [PubMed: 11297510] [MGI Ref ID J:68558]
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Purchasing Information
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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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