Symbol:	Nf1tm1Tyj
Name:	neurofibromatosis 1; targeted mutation 1, Tyler Jacks
MGI ID:	MGI:1857478
Synonyms:	Nf1-, Nf1n31
Gene:	Nf1   Location: Chr11:79153195-79395114 bp, + strand    Genetic Position: Chr11, 46.06 cM, cytoband B4-5

Germline Transmission:	Earliest citation of germline transmission: J:18542
Parent Cell Line:	D3 (ES Cell)
Strain of Origin:	129S2/SvPas

Allele Type:	Targeted (knock-out)
Mutations:	Insertion, Intragenic deletion
	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. (J:18542)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 2 strains available      Cell Lines: 0 lines available
Carrying any Nf1 Mutation:	17 strains or lines available

In Mice Carrying this Mutation:

8 assay results

Phenotypic Data by Genotype (show or hide all phenotypic details)

Genotype Allelic Composition Genetic Background     hm1    Nf1tm1Tyj/Nf1tm1Tyj involves: 129S2/SvPas nervous system abnormal neural crest cells (J:131914) 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 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 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 survival of these neural crest stem cells is improved under adverse culture conditions compared to cells from littermate controls embryogenesis abnormal neural crest cells (J:131914) 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 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 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 survival of these neural crest stem cells is improved under adverse culture conditions compared to cells from littermate controls Genotype Allelic Composition Genetic Background     hm2   Disease Model   Nf1tm1Tyj/Nf1tm1Tyj involves: 129S2/SvPas * C57BL/6 lethality/prenatal-perinatal embryonic lethality during organogenesis (J:18542) between E12.5 and E14 cardiovascular system abnormal cardiac muscle morphology (J:18542) myocardium, particularly of the ventricles, was lacy in appearance and thinner than normal double outlet heart right ventricle (J:18542) distended pericardium (J:18542) homeostasis/metabolism hydrops fetalis (J:18542) begin to exhibit edema at E12.5 muscle abnormal cardiac muscle morphology (J:18542) myocardium, particularly of the ventricles, was lacy in appearance and thinner than normal skin/coat/nails pallor (J:18542) Mouse Models of Human Disease Note Ref(s)   Models with phenotypic similarity to human diseases associated with human NF1. Watson Syndrome   J:18542   Genotype Allelic Composition Genetic Background     ht3    Nf1tm1Tyj/Nf1+ involves: 129S2/SvPas immune system abnormal mast cell physiology (J:142439) bone marrow derived mast cells have about a 25% faster proliferation rate than controls when cultured for three days with SCF these mast cells also have a two-thirds higher migration rate towards SCF in transwell assays than controls a similar higher migration rate to the skin is observed in vivo when SCF is administered increased mast cell degranulation (J:142439) the percent of degranulating mast cells in SCF-treated skin is almost 4 times that of controls Genotype Allelic Composition Genetic Background     ht4    Nf1tm1Tyj/Nf1+ involves: 129S2/SvPas * C57BL/6 tumorigenesis increased tumor incidence (J:18542) 75% of mice develop tumors over 27 months, including lymphomas, leukemias, lung adenocarcinomas, hepatomas, fibrosarcomas, neurofibrosarcoma, and adrenal tumors mice develop similar types of tumors seen in patients with neurofibromatosis, but do not present any other classical features of the disease adrenal tumor (J:18542) pheochromocytoma (J:18542) leukemia (J:18542) some heterozygotes developed lymphoid leukemia and myeloid leukemia hepatoma (J:18542) lung adenocarcinoma (J:18542) lymphoma (J:18542) fibrosarcoma (J:18542) neurofibrosarcoma (J:18542) Mouse Models of Human Disease Note Ref(s)   No similarity to expected human disease phenotype was found.1 NOT Neurofibromatosis, Type I; NF1   J:18542 1One or more human genes may be associated with the human disease. The mouse genotype may involve mutations in orthologous genes, but the phenotype did not resemble the human disease.   Genotype Allelic Composition Genetic Background     ht5   Disease Model   Nf1tm1Tyj/Nf1+ involves: 129S2/SvPas * C57BL/6J behavior/neurological abnormal spatial learning (J:38703) impairment in Morris Water Maze that was overcome with extensive training, however normal long term memory in cued fear conditioning test and normal nociception Mouse Models of Human Disease Note Ref(s)   Models with phenotypic similarity to human diseases associated with human NF1. Neurofibromatosis, Type I; NF1   J:38703   Genotype Allelic Composition Genetic Background     cn6    Nf1tm1Par/Nf1tm1Tyj Tg(Wnt1-cre)11Rth/0 involves: 129/Sv * C57BL/6 * CBA embryogenesis abnormal neural crest cell morphology (J:131914) increase in the frequency of neural crest stem cells in the sympathetic chain, dorsal root ganglia, and sciatic nerve at E13 but not at E17 to E19 nervous system abnormal neural crest cell morphology (J:131914) increase in the frequency of neural crest stem cells in the sympathetic chain, dorsal root ganglia, and sciatic nerve at E13 but not at E17 to E19 Genotype Allelic Composition Genetic Background     cn7    Nf1tm1Par/Nf1tm1Tyj Tg(P0-Cre)1Gth/0 involves: 129/Sv * FVB/N nervous system nervous system phenotype (J:131914) neural crest stem cells do not abnormally persist in the peripheral nervous system in adult mice tumorigenesis fibroma (J:131914) at 15 - 20 months of age, all 6 mice examined had plexiform neurofibromas compared to 0 fibromas in control littermates Genotype Allelic Composition Genetic Background     cn8    Nf1tm1Par/Nf1tm1Tyj Tg(Postn-cre)1Sjc/0 involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ life span/aging premature death (J:131914) only 6 of 32 mice survived beyond 4 weeks of age tumorigenesis tumorigenesis (J:131914) unlike mice crossed to Tg(P0-Cre)1Gth tumors are not seen in surviving adults embryogenesis abnormal neural crest cell morphology (J:131914) increase in the frequency of neural crest stem cells in the sympathetic chain and sciatic nerve, but not the gut, at E15 but not in surviving adults nervous system abnormal neural crest cell morphology (J:131914) increase in the frequency of neural crest stem cells in the sympathetic chain and sciatic nerve, but not the gut, at E15 but not in surviving adults Genotype Allelic Composition Genetic Background     cx9   Disease Model   Nf1tm1Tyj/Nf1tm1Tyj Rasa1tm1Paw/Rasa1tm1Paw either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6) or (involves: 129S1/Sv * 129X1/SvJ * CD-1) cardiovascular system abnormal heart morphology (J:29825) the heart and surrounding trunk are abnormal embryogenesis abnormal embryo turning (J:29825) embryo turning usually failed abnormal embryonic tissue morphology (J:29825) abnormal branchial arch morphology (J:29825) lacking or abnormal absent limb buds (J:29825) abnormal neural tube morphology/development (J:29825) localized regions of cell proliferation and outgrowth in the neural tube failure of somite differentiation (J:29825) fewer than 8 disorganized somites abnormal neural crest cell apoptosis (J:29825) cell death is widespread in migrating cranial neural crest abnormal extraembryonic tissue morphology (J:29825) enlarged allantois (J:29825) abnormal yolk sac morphology (J:29825) roughened appearance embryonic growth arrest (J:29825) arrested development around E8.5 hearing/vestibular/ear abnormal otic vesicle development (J:29825) otic placodes develop but do not develop into vesicles nervous system abnormal neural tube morphology/development (J:29825) localized regions of cell proliferation and outgrowth in the neural tube abnormal brain morphology (J:29825) abnormal forebrain morphology (J:29825) failure of forebrain structures to develop abnormal hindbrain morphology (J:29825) dorsal surface of the hindbrain failed to close cell death was widespread in the hindbrain abnormal midbrain morphology (J:29825) midbrain fails to develop craniofacial abnormal branchial arch morphology (J:29825) lacking or abnormal limbs/digits/tail absent limb buds (J:29825) Mouse Models of Human Disease Note Ref(s)   Models with phenotypic similarity to human diseases associated with human NF1. Neurofibromatosis, Type I; NF1   J:29825   Models with phenotypic similarity to human diseases not associated with human NF1. Capillary Malformation-Arteriovenous Malformation 1 J:29825 Parkes Weber Syndrome 1 J:29825 1RASA1 is associated with this disease in humans.   Genotype Allelic Composition Genetic Background     cx10   Disease Model   Nf1tm1Tyj/Nf1+ Trp53tm1Tyj/Trp53+ involves: 129/Sv * C57BL/6 life span/aging premature death (J:58876) cis-double heterozygotes die by 5 months of age and trans-double heterozygotes survive to the average age of 10 months tumorigenesis increased tumor incidence (J:58876) cis-double heterozygotes exhibit greater incidence of tumors than trans-double heterozygotes malignant peripheral nerve sheath tumors (J:58876) develop in cis-double heterozygotes, usually correlated with loss of one chromosome sarcoma (J:58876) 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 Mouse Models of Human Disease Note Ref(s)   Models with phenotypic similarity to human diseases associated with human NF1. Neurofibromatosis, Type I; NF1   J:58876   Genotype Allelic Composition Genetic Background     cx11    Nf1tm1Tyj/Nf1+ Trp53tm1Tyj/Trp53+ involves: 129S2/SvPas nervous system nervous system phenotype (J:131914) neural crest stem cells do not abnormally persist in the peripheral nervous system in adult mice tumorigenesis malignant peripheral nerve sheath tumors (J:131914) form by 6 months of age Genotype Allelic Composition Genetic Background     cx12    Nf1tm1Tyj/Nf1+ Pak1tm1Cher/Pak1tm1Cher involves: 129S2/SvPas immune system abnormal mast cell physiology (J:142439) bone marrow derived mast cells proliferate at 60% the rate as controls when cultured for three days with SCF migration rates and degranulation of mast cells in response to SCF-treatment is similar to wild-type controls Genotype Allelic Composition Genetic Background     cx13    Cdkn2atm2.1Rdp/Cdkn2atm2.1Rdp Nf1tm1Tyj/Nf1+ involves: 129S2/SvPas * 129S6/SvEvTac tumorigenesis tumorigenesis (J:131914) unlike other mice with at least one Nf1 allele, mice do not display malignant peripheral nerve sheath tumors or neurofibromas lymphoma (J:131914) hematopoietic neoplasms, especially lymphoma, are seen in some mice Genotype Allelic Composition Genetic Background     cx14    Cdkn2atm1Rdp/Cdkn2atm1Rdp Nf1tm1Tyj/Nf1+ involves: 129S2/SvPas * 129S6/SvEvTac life span/aging premature death (J:131914) virtually all mice die by 10 months of age tumorigenesis leukemia (J:131914) seen in some mice lymphoma (J:131914) significant frequency of hematopoietic neoplasms consisting mainly of lymphomas and histiocytic neoplasms with lower incidences of acute myeloid leukemias and myeloproliferative disease malignant peripheral nerve sheath tumors (J:131914) developed in 26% of mice in most cases these tumors are grossly evident by 4 to 6 months of age nervous system nervous system phenotype (J:131914) neural crest stem cells do not abnormally persist in the peripheral nervous system in adult mice Genotype Allelic Composition Genetic Background     cx15    Cdkn2atm1Rdp/Cdkn2a+ Nf1tm1Tyj/Nf1+ involves: 129S2/SvPas * 129S6/SvEvTac tumorigenesis malignant peripheral nerve sheath tumors (J:131914) seen at lower frequencies and greater age (over 1 year) compared to mice heterozygous for Nf1 and homozygous for Cdkn2a Genotype Allelic Composition Genetic Background     cx16   Disease Model   Nf1tm1Tyj/Nf1+ Trp53tm1Brd/Trp53+ involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6 life span/aging premature death (J:58877) cis-double heterozygotes died at 15 weeks and trans-double heterozygotes died at 25 weeks tumorigenesis fibrohistocytoma (J:58877) developed in cis-double heterozygotes lymphoma (J:58877) developed in cis-double heterozygotes neuroblastoma (J:58877) developed in cis-double heterozygotes carcinoma (J:58877) developed in cis-double heterozygotes malignant peripheral nerve sheath tumors (J:58877) developed in cis-double heterozygotes malignant triton tumors (J:58877) developed in cis-double heterozygotes sarcoma (J:58877) both cis- and trans-double heterozygotes developed sarcomas leiomyosarcoma (J:58877) developed in cis-double heterozygotes rhabdomyosarcoma (J:58877) developed in cis-double heterozygotes Mouse Models of Human Disease Note Ref(s)   Models with phenotypic similarity to human diseases associated with human NF1. Neurofibromatosis, Type I; NF1   J:58877   Genotype Allelic Composition Genetic Background     cx17    Nf1tm1Tyj/Nf1+ Trp53tm1Brd/Trp53tm1Brd involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6 lethality/postnatal postnatal lethality (J:58877) die as early as 3 weeks of age tumorigenesis lymphoma (J:58877) develop tumors, primarily lymphomas Genotype Allelic Composition Genetic Background     cx18   Disease Model   Grin1tm1Stl/Grin1+ Nf1tm1Tyj/Nf1+ involves: 129S2/SvPas * C57BL/6J behavior/neurological abnormal spatial learning (J:38703) spatial learning impairment in Morris Water Maze Test, however normal long term memory in cued fear conditioning test and normal nociception Mouse Models of Human Disease Note Ref(s)   Models with phenotypic similarity to human diseases associated with human NF1. Neurofibromatosis, Type I; NF1   J:38703   Genotype Allelic Composition Genetic Background     cx19    Nf1tm1Tyj/? Trp53tm1Tyj/? Mastr129S4/SvJae/? involves: 129S4/SvJae * C57BL/6J tumorigenesis increased resistance to tumor development (J:92444) astrocytoma resistance Genotype Allelic Composition Genetic Background     cx20    Nf1tm1Tyj/? Trp53tm1Tyj/? MastrC57BL/6J/? involves: 129S4/SvJae * C57BL/6J tumorigenesis malignant tumors (J:92444) astrocytoma susceptibility Genotype Allelic Composition Genetic Background     cx21    Nf1tm1Tyj/? Nstr1A/J/? Trp53tm1Tyj/? involves: A/J * C57BL/6J tumorigenesis increased resistance to tumor development (J:105038) resistance to peripheral nerve sheath tumors Genotype Allelic Composition Genetic Background     cx22    Nf1tm1Tyj/? Nstr1C57BL/6J/Nstr1C57BL/6J Trp53tm1Tyj/? involves: A/J * C57BL/6J tumorigenesis malignant peripheral nerve sheath tumors (J:105038) susceptibility to developing peripheral nerve sheath tumors Genotype Allelic Composition Genetic Background     cx23    Nf1tm1Tyj/? Nstr2A/J/? Trp53tm1Tyj/? involves: A/J * C57BL/6J tumorigenesis increased resistance to tumor development (J:105038) resistance to peripheral nerve sheath tumors

Mouse Models of Human Disease		Note	Genotype			Ref(s)
				Allelic Composition	Genetic Background
Models with phenotypic similarity to human diseases associated with human NF1.
Neurofibromatosis, Type I; NF1 OMIM ID: 162200			cx18	Grin1tm1Stl/Grin1+ Nf1tm1Tyj/Nf1+	involves: 129S2/SvPas * C57BL/6J	J:38703
			cx16	Nf1tm1Tyj/Nf1+ Trp53tm1Brd/Trp53+	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	J:58877
			cx10	Nf1tm1Tyj/Nf1+ Trp53tm1Tyj/Trp53+	involves: 129/Sv * C57BL/6	J:58876
			ht5	Nf1tm1Tyj/Nf1+	involves: 129S2/SvPas * C57BL/6J	J:38703
			cx9	Nf1tm1Tyj/Nf1tm1Tyj Rasa1tm1Paw/Rasa1tm1Paw	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6) or (involves: 129S1/Sv * 129X1/SvJ * CD-1)	J:29825
Watson Syndrome OMIM ID: 193520			hm2	Nf1tm1Tyj/Nf1tm1Tyj	involves: 129S2/SvPas * C57BL/6	J:18542
Models with phenotypic similarity to human diseases not associated with human NF1.
Capillary Malformation-Arteriovenous Malformation OMIM ID: 608354		1	cx9	Nf1tm1Tyj/Nf1tm1Tyj Rasa1tm1Paw/Rasa1tm1Paw	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6) or (involves: 129S1/Sv * 129X1/SvJ * CD-1)	J:29825
Parkes Weber Syndrome OMIM ID: 608355		1	cx9	Nf1tm1Tyj/Nf1tm1Tyj Rasa1tm1Paw/Rasa1tm1Paw	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6) or (involves: 129S1/Sv * 129X1/SvJ * CD-1)	J:29825
No similarity to expected human disease phenotype was found.2
NOT	Neurofibromatosis, Type I; NF1 OMIM ID: 162200		ht4	Nf1tm1Tyj/Nf1+	involves: 129S2/SvPas * C57BL/6	J:18542

¹RASA1 is associated with this disease in humans.
²One or more human genes may be associated with the human disease. The mouse genotype may involve mutations in orthologous genes, but the phenotype did not resemble the human disease.

Original:	J:18542 Jacks T et al., "Tumour predisposition in mice heterozygous for a targeted mutation in Nf1." Nat Genet 1994 Jul;7(3):353-61
All:	43 reference(s)