Phenotypes associated with this allele

• Allele Symbol: Nf1^tm1Fcr
• Allele Name: targeted mutation 1, Fredrick Cancer Research and Development Center
• Allele ID: MGI:1857444
• Summary: 18 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nf1^tm1Fcr/Nf1^tm1Fcr	either: (involves: 129S/SvEv) or (involves: 129S/SvEv * C57BL/6J)	MGI:2175141
hm2	Nf1^tm1Fcr/Nf1^tm1Fcr	involves: 129S/SvEv	MGI:3689631
ht3	Nf1^tm1Fcr/Nf1^tm1.1Par	involves: 129S/SvEv * 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:2176765
cn4	Nf1^tm1Fcr/Nf1^+ Pten^tm1Hwu/Pten^tm1Hwu Tg(Mx1-cre)1Cgn/0	B6.Cg-Tg(Mx1-cre)1Cgn Nf1^tm1Fcr Pten^tm1Hwu	MGI:5787929
cn5	Nf1^tm1Fcr/Nf1^tm1Par Pax3^tm1(cre)Joe/Pax3^+	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ	MGI:3689705
cn6	Nf1^tm1Par/Nf1^tm1Fcr Tg(GFAP-cre)#Gtm/0	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:4838320
cn7	Gt(ROSA)26Sor^tm1Fia/Gt(ROSA)26Sor^+ Nf1^tm1Fcr/Nf1^tm1Par Tg(Tek-cre)1Ywa/0	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3689708
cn8	Nf1^tm1Fcr/Nf1^tm1Par Tg(Tek-cre)1Ywa/0	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3689709
cn9	Nf1^tm1Fcr/Nf1^+ Tsc1^tm1Djk/Tsc1^tm1Djk Tg(GFAP-cre)#Gtm/0	involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA	MGI:5292550
cn10	Nf1^tm1Fcr/Nf1^+ Tg(GFAP-cre)#Gtm/0	involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA	MGI:5292552
cn11	Nf1^tm1Fcr/Nf1^tm1Fcr Trp53^tm1Elee/Trp53^tm1Elee Tg(GFAP-cre)25Mes/0	involves: 129S/SvEv * 129S4/SvJae * FVB/N	MGI:3849179
cn12	Gt(ROSA)26Sor^tm1Fia/Gt(ROSA)26Sor^+ Hprt1^tm1(CMV-cre)Brd/Hprt1^+ Nf1^tm1Fcr/Nf1^tm1Fcr	involves: 129S/SvEv * 129S/SvEvBrd	MGI:3689632
cn13	Gt(ROSA)26Sor^tm1Fia/Gt(ROSA)26Sor^tm1Fia Hprt1^tm1(CMV-cre)Brd/Hprt1^+ Nf1^tm1Fcr/Nf1^tm1Fcr	involves: 129S/SvEv * 129S/SvEvBrd	MGI:3689697
cx14	Nf1^tm1Fcr/Nf1^+ Trp53^tm1Brd/Trp53^+	B6.129-Trp53^tm1Brd Nf1^tm1Fcr	MGI:5485355
cx15	Nf1^tm1Fcr/Nf1^+ Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S/SvEv * 129S2/SvPas * C57BL/6	MGI:3580070
cx16	Nf1^tm1Fcr/Nf1^+ Trp53^tm1Tyj/Trp53^+	involves: 129S/SvEv * 129S2/SvPas * C57BL/6	MGI:3580069
cx17	Egfr^wa2/Egfr^+ Nf1^tm1Fcr/Nf1^+ Trp53^tm1Brd/Trp53^+	involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * C57BL/6JEi * C3H/HeSnJ	MGI:5485354
cx18	Nf1^tm1Fcr/Nf1^+ Tg(Cnp-EGFR)10Nrat/0	involves: 129S/SvEv * C57BL/6 * SJL	MGI:5485353

Genotype
MGI:2175141

hm1

• Allelic Composition: Nf1^tm1Fcr/Nf1^tm1Fcr
• Genetic Background: either: (involves: 129S/SvEv) or (involves: 129S/SvEv * C57BL/6J)

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:18048 )

• all die by E14.5

cardiovascular system

abnormal vein morphology ( J:18048 )

• show distended veins

blood vessel congestion ( J:18048 )

disorganized myocardium ( J:18048 )

• show disoriented and poorly developed myocardial fibers

persistent truncus arteriosus ( 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 development ( J:18048 )

abnormal fetal atrioventricular canal morphology ( J:18048 )

• at E13.5, the atrioventricular canal is composed of loosely arranged endothelial cells that lack the typical cellular density

abnormal atrioventricular cushion morphology ( 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 atrioventricular cushion size ( J:18048 )

• considerably larger at E13.5

ventricular septal defect ( J:18048 )

• exhibit only a rudimentary septum near the apex that is exculsively muscular

globular heart ( J:18048 )

heart hypoplasia ( J:18048 )

abnormal heart valve morphology ( J:18048 )

• cardiac valve abnormalities at E13.5

abnormal mitral valve cusp morphology ( J:18048 )

• leaflets of the mitral valve remain poorly condensed at E13.5

pericardial effusion ( J:18048 )

liver hemorrhage ( J:18048 )

• seen at E13.5

liver/biliary system

liver hemorrhage ( J:18048 )

• seen at E13.5

delayed hepatic development ( J:18048 )

• 18- to 24-hr delay in hepatic development

liver hypoplasia ( J:18048 )

• seen at E13.5

focal hepatic necrosis ( J:18048 )

• seen at E13.5

pale liver ( J:18048 )

muscle

abnormal muscle morphology ( J:18048 )

• musculature of the stomach, the three layers of the abdominal musculature, and the muscles of the shoulder girdle are thinner

disorganized myocardium ( J:18048 )

• show disoriented and poorly developed myocardial fibers

delayed muscle development ( J:18048 )

• 18- to 24-hour delay in development of skeletal muscle

skeletal muscle hypoplasia ( J:18048 )

• skeletal muscle throughout the body is hypoplastic at E13.5

renal/urinary system

decreased renal glomerulus number ( J:18048 )

• reduced number of glomeruli at E13.5, due to developmental delay

abnormal metanephros morphology ( J:18048 )

• a retardation of cephalad repositioning is noted at E13.5

delayed kidney development ( J:18048 )

• 18- to 24-hr delay in renal development

• in the metanephros, display a retardation of cephalad repositioning at E13.5

vision/eye

microphthalmia ( J:18048 )

nervous system

paravertebral ganglia hyperplasia ( J:18048 )

prevertebral ganglia hyperplasia ( J:18048 )

exencephaly ( J:18048 )

• seen in about 6.3% of homozygotes

growth/size/body

enlarged chest ( J:18048 )

• display a chest bulge

megacephaly ( J:18048 )

homeostasis/metabolism

pericardial effusion ( J:18048 )

edema ( J:18048 )

• systemic edema

pleural effusion ( J:18048 )

immune system

abnormal lymphatic vessel morphology ( J:18048 )

• show distended lymphatics

respiratory system

pleural effusion ( J:18048 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:18048

Genotype
MGI:3689631

hm2

• Allelic Composition: Nf1^tm1Fcr/Nf1^tm1Fcr
• Genetic Background: involves: 129S/SvEv

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:114455 )

• homozygotes die by E13.5

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:114455 )

• active Ras levels are elevated in homozygotes

Genotype
MGI:2176765

ht3

• Allelic Composition: Nf1^tm1Fcr/Nf1^tm1.1Par
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * 129S2/SvPas * 129X1/SvJ

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:68558 )

• die at E13.5

cardiovascular system

enlarged heart ( J:68558 )

hemorrhage ( J:68558 )

homeostasis/metabolism

edema ( J:68558 )

• peripheral edema

vision/eye

decreased eye pigmentation ( J:68558 )

• small unpigmented eyes

microphthalmia ( J:68558 )

pigmentation

decreased eye pigmentation ( J:68558 )

• small unpigmented eyes

growth/size/body

enlarged heart ( J:68558 )

Genotype
MGI:5787929

cn4

• Allelic Composition: Nf1^tm1Fcr/Nf1⁺; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Mx1-cre)1Cgn/0
• Genetic Background: B6.Cg-Tg(Mx1-cre)1Cgn Nf1^tm1Fcr Pten^tm1Hwu

mortality/aging

premature death ( J:232645 )

• mice injected intraperitoneally with poly(I:C) at P8 to induce loss of Pten all die at 20 to 35 days of age

hematopoietic system

abnormal hemopoiesis ( J:232645 )

• mice injected with poly(I:C) at P8 develop myeloproliferative neoplasm with clinical manifestations of Juvenile myelomonocytic leukemia at 2-3 weeks post induction

anemia ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit anemia 2-3 weeks post induction

decreased bone marrow cell number ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit reduced total cell numbers in bone marrow at 2-3 weeks post induction

decreased hemoglobin content ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit decreased hemoglobin 2-3 weeks post induction

thrombocytosis ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased platelets 2-3 weeks post induction

decreased lymphocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show a reduction in lymphocytes 2-3 weeks post induction

decreased B cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased B-cell (CD19+) populations in PB and spleen at 2-3 weeks post induction

decreased T cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased T-cell (CD3e+) populations in PB and spleen at 2-3 weeks post induction

increased leukocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit a modest elevation in white blood cells 2-3 weeks post poly(I:C) treatment

increased granulocyte number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in granulocytes in bone marrow, blood, and spleen 2-3 weeks post induction

increased macrophage cell number ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased macrophages in bone marrow, blood, and spleen at 2-3 weeks post induction

increased monocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in monocytes in bone marrow, blood, and spleen 2-3 weeks post induction

abnormal hematopoietic stem cell morphology ( J:232645 )

• bone marrow of mice injected with poly(I:C) at P8 shows decreased hematopoietic progenitor cells, including LIN-, LIN-Sca1-1-, cKit+, and LIN-Sca1-1+cKit+, are decreased, with less apoptosis

• spleen of mice injected with poly(I:C) at P8 shows an increase in hematopoietic progenitor cells

abnormal spleen morphology ( J:232645 )

• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage and granulocyte infiltration in the spleen at 2-3 weeks post induction

• spleen of mice injected with poly(I:C) at P8 shows an increase in hematopoietic progenitor cells

enlarged spleen ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen size

increased spleen weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen weight

immune system

decreased lymphocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show a reduction in lymphocytes 2-3 weeks post induction

decreased B cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased B-cell (CD19+) populations in PB and spleen at 2-3 weeks post induction

decreased T cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show decreased T-cell (CD3e+) populations in PB and spleen at 2-3 weeks post induction

increased leukocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit a modest elevation in white blood cells 2-3 weeks post poly(I:C) treatment

increased granulocyte number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in granulocytes in bone marrow, blood, and spleen 2-3 weeks post induction

increased macrophage cell number ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased macrophages in bone marrow, blood, and spleen at 2-3 weeks post induction

increased monocyte cell number ( J:232645 )

• mice injected with poly(I:C) at P8 show an elevation in monocytes in bone marrow, blood, and spleen 2-3 weeks post induction

abnormal spleen morphology ( J:232645 )

• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage and granulocyte infiltration in the spleen at 2-3 weeks post induction

• spleen of mice injected with poly(I:C) at P8 shows an increase in hematopoietic progenitor cells

enlarged spleen ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen size

increased spleen weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen weight

liver/biliary system

abnormal liver morphology ( J:232645 )

• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage infiltration in the liver at 2-3 weeks post induction

enlarged liver ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased liver size

increased liver weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased liver weight

neoplasm

increased tumor incidence ( J:232645 )

• mice injected with poly(I:C) at P8 develop myeloproliferative neoplasm with clinical manifestations of Juvenile myelomonocytic leukemia at 2-3 weeks post induction

• recipient mice transplanted with bone marrow nucleated cells from mutants develop an indolent myelodysplastic syndrome or myeloproliferative neoplasm by 8 weeks posttransplantation

• mice injected with poly(I:C) at 6 weeks of age develop a transient myeloproliferative neoplasm after 3 weeks post induction and 1/7 transform to T-ALL

increased T cell acute lymphoblastic leukemia incidence ( J:232645 )

• mice injected with poly(I:C) at 6 weeks of age develop a transient myeloproliferative neoplasm after 3 weeks post induction and 1/7 transform to T-ALL

respiratory system

abnormal lung morphology ( J:232645 )

• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage infiltration in the spleens, livers, and lungs at 2-3 weeks post induction

skeleton

abnormal bone marrow morphology ( J:232645 )

• mice injected with poly(I:C) at P8 show increases in monocytes/macrophages and granulocytes in the bone marrow at 2-3 weeks post induction

• bone marrow of mice injected with poly(I:C) at P8 shows decreased hematopoietic progenitor cells, including LIN-, LIN-Sca1-1-, cKit+, and LIN-Sca1-1+cKit+, are decreased, with less apoptosis

growth/size/body

enlarged liver ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased liver size

increased liver weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased liver weight

enlarged spleen ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen size

increased spleen weight ( J:232645 )

• mice injected with poly(I:C) at P8 exhibit increased spleen weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
juvenile myelomonocytic leukemia		DOID:0050458	OMIM:607785	J:232645

Genotype
MGI:3689705

cn5

• Allelic Composition: Nf1^tm1Fcr/Nf1^tm1Par; Pax3^tm1(cre)Joe/Pax3⁺
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ

mortality/aging

neonatal lethality, complete penetrance ( J:114455 )

• pups die at birth

endocrine/exocrine glands

adrenal medulla hyperplasia ( J:114455 )

• medulla is overgrown compared with wild-type

nervous system

abnormal somatic sensory system morphology ( J:114455 )

• peripheral ganglia are massively enlarged in newborns

Genotype
MGI:4838320

cn6

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Fcr; Tg(GFAP-cre)#Gtm/0
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

hematopoietic system

abnormal microglial cell morphology ( J:165209 )

• at 9 months of age, mutants have significantly more microglia than controls; microglia are in the optic gliomas

immune system

abnormal microglial cell morphology ( J:165209 )

• at 9 months of age, mutants have significantly more microglia than controls; microglia are in the optic gliomas

nervous system

abnormal microglial cell morphology ( J:165209 )

• at 9 months of age, mutants have significantly more microglia than controls; microglia are in the optic gliomas

increased glioma incidence ( J:165209 )

• mice develop optic gliomas in the optic chiasm/nerves

• optic gliomas appear as gross thickenings and enlargements of the pre-chiasmic nerve at 9 months of age

abnormal astrocyte morphology ( J:165209 )

• irregularly shaped and thickened astrocytes are seen in the pre-chiasmatic optic nerves

retina ganglion cell degeneration ( J:165209 )

• retinal ganglion cell loss in the middle and peripheral region

abnormal optic nerve morphology ( J:165209 )

• optic gliomas form in the pre-chiasmatic optic nerve/optic chiasm, with increased vascularization to the area, abnormally shaped and thickened astrocytes, increase in microglia, and axonal and myelin degeneration

• mice exhibit abnormal optic nerve axon organization

abnormal optic chiasm morphology ( J:165209 )

• the optic chiasm/nerves at 9 months of age appear as gross fusiform enlargements that result in optic gliomas

• increase in vascularization in the pre-chiasmatic optic nerve and optic chiasm (and in the optic glioma)

axon degeneration ( J:165209 )

• axonal and myelin degeneration are seen in the optic nerve

abnormal astrocyte physiology ( J:165209 )

• increase in neoplastic astrocyte proliferation in the optic glioma

abnormal myelination ( J:165209 )

• disruption of the myelin is seen in the optic nerve, including degeneration and hypermyelination

hypermyelination ( J:165209 )

• hypermyelination is seen in the optic nerve

neoplasm

increased glioma incidence ( J:165209 )

• mice develop optic gliomas in the optic chiasm/nerves

• optic gliomas appear as gross thickenings and enlargements of the pre-chiasmic nerve at 9 months of age

vision/eye

retina ganglion cell degeneration ( J:165209 )

• retinal ganglion cell loss in the middle and peripheral region

abnormal optic nerve morphology ( J:165209 )

• optic gliomas form in the pre-chiasmatic optic nerve/optic chiasm, with increased vascularization to the area, abnormally shaped and thickened astrocytes, increase in microglia, and axonal and myelin degeneration

• mice exhibit abnormal optic nerve axon organization

abnormal optic chiasm morphology ( J:165209 )

• the optic chiasm/nerves at 9 months of age appear as gross fusiform enlargements that result in optic gliomas

• increase in vascularization in the pre-chiasmatic optic nerve and optic chiasm (and in the optic glioma)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:165209

Genotype
MGI:3689708

cn7

• Allelic Composition: Gt(ROSA)26Sor^tm1Fia/Gt(ROSA)26Sor⁺; Nf1^tm1Fcr/Nf1^tm1Par; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

mortality/aging

prenatal lethality, complete penetrance ( J:114455 )

• 2 embryos are found at later stages, after expected midgestation lethality from cardiovascular failure

hematopoietic system

abnormal spleen morphology ( J:114455 )

• mice display moderate splenic enlargement and partial rescue of splenic architecture

• germinal centers are present

• splenic fibrosis is not observed

immune system

abnormal spleen morphology ( J:114455 )

• mice display moderate splenic enlargement and partial rescue of splenic architecture

• germinal centers are present

• splenic fibrosis is not observed

nervous system

abnormal dorsal root ganglion morphology ( J:114455 )

• marked enlargement of dorsal root ganglia and other neural crest derived tissues is observed

Genotype
MGI:3689709

cn8

• Allelic Composition: Nf1^tm1Fcr/Nf1^tm1Par; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

hematopoietic system

abnormal spleen morphology ( J:114455 )

• normal splenic architecture is lost

enlarged spleen ( J:114455 )

• mice show markedly enlarged spleens due to overgrowth of granulocytic precursors

absent spleen germinal center ( J:114455 )

• germinal centers are absent

spleen fibrosis ( J:114455 )

• splenic fibrosis is observed

immune system

abnormal spleen morphology ( J:114455 )

• normal splenic architecture is lost

enlarged spleen ( J:114455 )

• mice show markedly enlarged spleens due to overgrowth of granulocytic precursors

absent spleen germinal center ( J:114455 )

• germinal centers are absent

spleen fibrosis ( J:114455 )

• splenic fibrosis is observed

growth/size/body

enlarged spleen ( J:114455 )

• mice show markedly enlarged spleens due to overgrowth of granulocytic precursors

Genotype
MGI:5292550

cn9

• Allelic Composition: Nf1^tm1Fcr/Nf1⁺; Tsc1^tm1Djk/Tsc1^tm1Djk; Tg(GFAP-cre)#Gtm/0
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA

mortality/aging

premature death ( J:176586 )

• most mice die before 3 months of age

neoplasm

neoplasm ( J:176586 )

N • mice do not develop gliomas

Genotype
MGI:5292552

cn10

• Allelic Composition: Nf1^tm1Fcr/Nf1⁺; Tg(GFAP-cre)#Gtm/0
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA

Nf1^tm1Fcr/Nf1⁺ Tg(GFAP-cre)#Gtm/0 mice develop prechiasmatic optic nerve and chiasmal gliomas

nervous system

abnormal neuron proliferation ( J:176586 )

• cell proliferation in the optic nerve is increased compared to in wild-type mice

increased glioma incidence ( J:176586 )

• optic gliomas

abnormal optic nerve morphology ( J:176586 )

• kinking of the prechiasmatic optic nerves

increased optic chiasm size ( J:176586 )

• enlarged

neoplasm

increased glioma incidence ( J:176586 )

• optic gliomas

vision/eye

abnormal optic nerve morphology ( J:176586 )

• kinking of the prechiasmatic optic nerves

increased optic chiasm size ( J:176586 )

• enlarged

cellular

abnormal neuron proliferation ( J:176586 )

• cell proliferation in the optic nerve is increased compared to in wild-type mice

Genotype
MGI:3849179

cn11

• Allelic Composition: Nf1^tm1Fcr/Nf1^tm1Fcr; Trp53^tm1Elee/Trp53^tm1Elee; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * FVB/N

mortality/aging

premature death ( J:149662 )

• all mice die prior to 200 days

neoplasm

increased glioma incidence ( J:149662 )

• 70% of gliomas exhibit necrosis, a feature of human glioblastoma multiforme

• tumors are relatively homogeneous histological and in lineage marker expression

decreased tumor latency ( J:149662 )

• all mice develop astrocytic gliomas with shorter latency than observed in Trp53^tm1Elee/Trp53^tm1Tyj Tg(GFAP-cre)25Mes or Trp53^tm1Elee/ Trp53^tm1Elee Tg(GFAP-cre)25Mes mice

nervous system

increased glioma incidence ( J:149662 )

• 70% of gliomas exhibit necrosis, a feature of human glioblastoma multiforme

• tumors are relatively homogeneous histological and in lineage marker expression

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
glioblastoma		DOID:3068		J:149662

Genotype
MGI:3689632

cn12

• Allelic Composition: Gt(ROSA)26Sor^tm1Fia/Gt(ROSA)26Sor⁺; Hprt1^{tm1(CMV-cre)Brd}/Hprt1⁺; Nf1^tm1Fcr/Nf1^tm1Fcr
• Genetic Background: involves: 129S/SvEv * 129S/SvEvBrd

mortality/aging

prenatal lethality, incomplete penetrance ( J:114455 )

♀ • some mice (5/208) survive to birth while all Nf1-null homozygotes expressing either Gt(ROSA)26Sor^tm1Fia or Hprt1^{tm1(CMV-cre)Brd} die prior to birth

nervous system

abnormal sympathetic ganglion morphology ( J:114455 )

♀ • massively enlarged

abnormal somatic sensory system morphology ( J:114455 )

♀ • peripheral ganglia are massively enlarged in newborns

abnormal dorsal root ganglion morphology ( J:114455 )

♀ • enormous paraspinal masses arise from the dorsal root ganglia

endocrine/exocrine glands

adrenal medulla hyperplasia ( J:114455 )

♀ • medulla is overgrown compared with wild-type, with cortical effacement and tumor-like medullary protrusion

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:114455 )

♀ • elevate Ras levels return to wild-type levels by E12.5 with expression of Gt(ROSA)26Sor^tm1Fia

Genotype
MGI:3689697

cn13

• Allelic Composition: Gt(ROSA)26Sor^tm1Fia/Gt(ROSA)26Sor^tm1Fia; Hprt1^{tm1(CMV-cre)Brd}/Hprt1⁺; Nf1^tm1Fcr/Nf1^tm1Fcr
• Genetic Background: involves: 129S/SvEv * 129S/SvEvBrd

nervous system

abnormal somatic sensory system morphology ( J:114455 )

♀ • peripheral ganglia are massively enlarged in newborns

Genotype
MGI:5485355

cx14

• Allelic Composition: Nf1^tm1Fcr/Nf1⁺; Trp53^tm1Brd/Trp53⁺
• Genetic Background: B6.129-Trp53^tm1Brd Nf1^tm1Fcr

nervous system

increased brain tumor incidence ( J:95933 )

• develop sarcomas and brain tumors as early as 15 weeks of age

mortality/aging

decreased tumor-free survival time ( J:95933 )

• mice that develop malignant tumors die by 26 weeks of age

neoplasm

increased malignant tumor incidence ( J:95933 )

• 11 of 19 (57.9%) mice develop malignant tumors and die by 26 weeks of age

increased sarcoma incidence ( J:95933 )

• develop sarcomas and brain tumors as early as 15 weeks of age

increased brain tumor incidence ( J:95933 )

• develop sarcomas and brain tumors as early as 15 weeks of age

Genotype
MGI:3580070

cx15

• Allelic Composition: Nf1^tm1Fcr/Nf1⁺; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6

mortality/aging

postnatal lethality, incomplete penetrance ( J:58877 )

• die as early as 3 weeks of age

neoplasm

increased lymphoma incidence ( J:58877 )

• develop tumors, primarily lymphomas

Genotype
MGI:3580069

cx16

• Allelic Composition: Nf1^tm1Fcr/Nf1⁺; Trp53^tm1Tyj/Trp53⁺
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:58877 )

• cis-double heterozygotes died at 15 weeks and trans-double heterozygotes died at 25 weeks

neoplasm

increased fibrohistocytoma incidence ( J:58877 )

• developed in cis-double heterozygotes

increased lymphoma incidence ( J:58877 )

• developed in cis-double heterozygotes

increased neuroblastoma incidence ( J:58877 )

• developed in cis-double heterozygotes

increased carcinoma incidence ( J:58877 )

• developed in cis-double heterozygotes

increased malignant triton tumor incidence ( J:58877 )

• developed in cis-double heterozygotes

increased sarcoma incidence ( J:58877 )

• both cis- and trans-double heterozygotes developed sarcomas

increased leiomyosarcoma incidence ( J:58877 )

• developed in cis-double heterozygotes

increased rhabdomyosarcoma incidence ( J:58877 )

• developed in cis-double heterozygotes

increased neurofibrosarcoma incidence ( J:58877 )

• developed in cis-double heterozygotes

integument

increased fibrohistocytoma incidence ( J:58877 )

• developed in cis-double heterozygotes

muscle

increased leiomyosarcoma incidence ( J:58877 )

• developed in cis-double heterozygotes

increased rhabdomyosarcoma incidence ( J:58877 )

• developed in cis-double heterozygotes

nervous system

increased neuroblastoma incidence ( J:58877 )

• developed in cis-double heterozygotes

increased neurofibrosarcoma incidence ( J:58877 )

• developed in cis-double heterozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:58877

Genotype
MGI:5485354

cx17

• Allelic Composition: Egfr^wa2/Egfr⁺; Nf1^tm1Fcr/Nf1⁺; Trp53^tm1Brd/Trp53⁺
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * C57BL/6JEi * C3H/HeSnJ

neoplasm

decreased tumor incidence ( J:95933 )

• only 1 of 17 (5.9%) mice develop a tumor, a spindle cell tumor compared to 57.9% of double heterozygous Nf1 and Trp53 mutants; this mouse was sacrificed at 21 weeks of age

Genotype
MGI:5485353

cx18

• Allelic Composition: Nf1^tm1Fcr/Nf1⁺; Tg(Cnp-EGFR)10Nrat/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * SJL

nervous system

abnormal nervous system morphology ( J:95933 )

• mutants exhibit similar diffuse nerve enlargement as in single Tg(Cnp-EGFR)10Nrat mice

abnormal somatic nervous system morphology ( J:95933 )

• saphenous nerves are larger at 4 months of age compared to wild-type mice but similar in size to those in single Tg(Cnp-EGFR)10Nrat mice

neoplasm

decreased tumor incidence ( J:95933 )

• no tumors are detected compared to single Tg(Cnp-EGFR)10Nrat mice