Phenotypes associated with this allele

• Allele Symbol: Nf1^tm1Par
• Allele Name: targeted mutation 1, Luis F Parada
• Allele ID: MGI:2176057
• Summary: 28 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Nf1^tm1Par/Nf1^tm1Par	involves: 129S1/Sv * 129X1/SvJ	MGI:5292548
cn2	Lrrc17^tm1Nik/Lrrc17^+ Nf1^tm1Par/Nf1^tm1Par Srpk2^tm1Nik/Srpk2^+ Tg(Mx1-cre)1Cgn/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:4460776
cn3	Nf1^tm1Par/Nf1^+ Pten^tm1Hwu/Pten^+ Trp53^tm1Tyj/Trp53^+ Tg(GFAP-cre)25Mes/0	involves: 129S1/Sv * 129S2/SvPas * 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4840094
cn4	Nf1^tm1Par/Nf1^tm1Tyj Tg(Postn-cre)1Sjc/0	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3776057
cn5	Nf1^tm1Par/Nf1^+ Trp53^tm1Tyj/Trp53^+ Tg(GFAP-cre)25Mes/0	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * FVB/N	MGI:4840090
cn6	Nf1^tm1Par/Nf1^+ Pten^tm1Hwu/Pten^+ Tg(Gfap-cre)77.6Mvs/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6NHsd	MGI:4849443
cn7	Nf1^tm1Par/Nf1^+ Pten^tm1Hwu/Pten^+ Trp53^tm1Elee/Trp53^+ Tg(GFAP-cre)25Mes/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4840096
cn8	Nf1^tm1Par/Nf1^+ Trp53^tm1Elee/Trp53^+ Tg(GFAP-cre)25Mes/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4840095
cn9	Cdkn2a^tm4Rdp/Cdkn2a^tm4Rdp Nf1^tm1Par/Nf1^tm1Par	involves: 129S1/Sv * 129X1/SvJ	MGI:5792147
cn10	Nf1^tm1Par/Nf1^tm1Par Tg(Mpz-cre)94Imeg/0	involves: 129S1/Sv * 129X1/SvJ	MGI:3710235
cn11	Nf1^tm1Par/Nf1^tm1Par Tg(Gfap-cre)77.6Mvs/0	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6NHsd	MGI:4849442
cn12	Nf1^tm1Par/Nf1^tm1Par H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3710237
cn13	Nf1^tm1Par/Nf1^tm1Par Tg(Syn1-cre)671Jxm/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:2176767
cn14	Nf1^tm1Par/Nf1^tm1Par Tg(Mx1-cre)1Cgn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:5544056
cn15	Nf1^tm1Par/Nf1^tm1Par Tg(Fabp7-cre,-lacZ)3Gtm/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3810648
cn16	Nf1^tm1Par/Nf1^+ Tg(Fabp7-cre,-lacZ)3Gtm/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3810649
cn17	Gt(ROSA)26Sor^tm1Fia/Gt(ROSA)26Sor^+ Nf1^tm1Par/Nf1^tm1Par Tg(Fabp7-cre,-lacZ)3Gtm/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3810651
cn18	Nf1^tm1Par/Nf1^tm1Par Tg(Prrx1-cre)1Cjt/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * C57BL/6N * SJL/J	MGI:5493228
cn19	Nf1^tm1Par/Nf1^tm1Par Tg(Prrx1-cre)1Cjt/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J	MGI:5492109
cn20	Nf1^tm1Par/Nf1^tm1Par Tg(Pax3-cre)1Joe/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3710236
cn21	Nf1^tm1Par/Nf1^tm1Par Tg(Tek-cre)1Ywa/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3710234
cn22	Nf1^tm1Fcr/Nf1^tm1Par Pax3^tm1(cre)Joe/Pax3^+	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ	MGI:3689705
cn23	Nf1^tm1Par/Nf1^tm1Fcr Tg(GFAP-cre)#Gtm/0	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:4838320
cn24	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
cn25	Nf1^tm1Fcr/Nf1^tm1Par Tg(Tek-cre)1Ywa/0	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3689709
cn26	Nf1^tm1Par/Nf1^tm1Tyj H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129/Sv * C57BL/6 * CBA	MGI:3776056
cn27	Nf1^tm1Par/Nf1^tm1Tyj Tg(Mpz-cre)1Brn/0	involves: 129/Sv * FVB/N	MGI:3776064
cx28	Nf1^tm1Par/Nf1^tm1Par Rnf7^Gt(XE423)Byg/Rnf7^Gt(XE423)Byg	involves: 129 * C57BL/6	MGI:5301658

Genotype
MGI:5292548

cn1

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

nervous system

abnormal astrocyte physiology ( J:176586 )

• astrocytes transfected with a cre-expresing adenovirus exhibit increased proliferation compared to in control cells

Genotype
MGI:4460776

cn2

• Allelic Composition: Lrrc17^tm1Nik/Lrrc17⁺; Nf1^tm1Par/Nf1^tm1Par; Srpk2^tm1Nik/Srpk2⁺; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

mortality/aging

premature death ( J:161558 )

• in pIpC-treated mice with the same timing as in pIpC-treated Nf1^tm1Par/Nf1^tm1Par Tg(Mx1-cre)1Cgn mice

immune system

increased leukocyte cell number ( J:161558 )

• pIpC-treated mice develop myeloproliferative disorder with anemia unlike wild-type mice that is similar to in pIpC-treated Nf1^tm1Par/Nf1^tm1Par Tg(Mx1-cre)1Cgn mice

hematopoietic system

increased leukocyte cell number ( J:161558 )

• pIpC-treated mice develop myeloproliferative disorder with anemia unlike wild-type mice that is similar to in pIpC-treated Nf1^tm1Par/Nf1^tm1Par Tg(Mx1-cre)1Cgn mice

Genotype
MGI:4840094

cn3

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Pten^tm1Hwu/Pten⁺; Trp53^tm1Tyj/Trp53⁺; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S4/SvJae * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:134611 )

• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity

behavior/neurological

increased startle reflex ( J:134611 )

• exaggerated startle response

ataxia ( J:134611 )

• ataxic gait

unidirectional circling ( J:134611 )

seizures ( J:134611 )

• generalized motor seizures

nervous system

seizures ( J:134611 )

• generalized motor seizures

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas

• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1^tm1Par and Trp53^tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes

neoplasm

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas

• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1^tm1Par and Trp53^tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant astrocytoma		DOID:3069		J:134611

Genotype
MGI:3776057

cn4

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Tyj; Tg(Postn-cre)1Sjc/0
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

mortality/aging

premature death ( J:131914 )

• only 6 of 32 mice survived beyond 4 weeks of age

neoplasm

neoplasm ( J:131914 )

N • unlike mice crossed to Tg(P0-Cre)1Gth tumors are not seen in surviving adults

embryo

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
MGI:4840090

cn5

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Trp53^tm1Tyj/Trp53⁺; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:134611 )

• mutants survive up to 8 weeks beyond initial appearance of symptoms

neoplasm

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• complete penetrance of malignant astrocytomas

• gliomas from asymptomatic mutants are primarily classified as grade 2 astocytomas

• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci

nervous system

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• complete penetrance of malignant astrocytomas

• gliomas from asymptomatic mutants are primarily classified as grade 2 astocytomas

• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant astrocytoma		DOID:3069		J:134611

Genotype
MGI:4849443

cn6

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Pten^tm1Hwu/Pten⁺; Tg(Gfap-cre)77.6Mvs/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6NHsd

neoplasm

neoplasm ( J:154673 )

N • mutants do not develop tumors

Genotype
MGI:4840096

cn7

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Pten^tm1Hwu/Pten⁺; Trp53^tm1Elee/Trp53⁺; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:134611 )

• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity

behavior/neurological

increased startle reflex ( J:134611 )

• exaggerated startle response

ataxia ( J:134611 )

• ataxic gait

unidirectional circling ( J:134611 )

seizures ( J:134611 )

• generalized motor seizures

nervous system

seizures ( J:134611 )

• generalized motor seizures

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• mutants develop astrocytomas

• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci

neoplasm

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• mutants develop astrocytomas

• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci

Genotype
MGI:4840095

cn8

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Trp53^tm1Elee/Trp53⁺; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:134611 )

• mutants survive up to 8 weeks beyond initial appearance of symptoms

behavior/neurological

increased startle reflex ( J:134611 )

• exaggerated startle response

ataxia ( J:134611 )

• ataxic gait

unidirectional circling ( J:134611 )

seizures ( J:134611 )

• generalized motor seizures

nervous system

seizures ( J:134611 )

• generalized motor seizures

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• mutants develop astrocytomas

• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci

neoplasm

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• mutants develop astrocytomas

• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant astrocytoma		DOID:3069		J:134611

Genotype
MGI:5792147

cn9

• Allelic Composition: Cdkn2a^tm4Rdp/Cdkn2a^tm4Rdp; Nf1^tm1Par/Nf1^tm1Par
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

neoplasm

increased sarcoma incidence ( J:234760 )

• mice injected intramuscularly with an adenovirus expressing cre recombinase (Ad-Cre) develop soft-tissue sarcomas in the region 3 to 12 months after cre exposure

• intramuscular injections of Ad-cre generates a spectrum of high-grade spindle cell sarcomas, including rhabdomyosarcoma and undifferentiated pleomorphic sarcoma

• tumors from both intramuscular and sciatic nerve Ad-Cre injected mice show significant infiltration of mast cells

• tumors arising from intramuscular Ad-Cre injection show higher proliferation than tumors arising from sciatic nerve Ad-Cre injection

• treatment of tumor cells isolated from intramuscularly Ad-Cre injected mice with the MEK inhibitor PD325901results in decreases colony-forming units and cell proliferation

• treatment of Ad-Cre intramuscularly injected mice with the MEK inhibitor PD325901 delays tumor growth, reduces proliferative index of tumors, and decreases CD31+ microvessel density but does not alter mast cell levels in tumors

increased rhabdomyosarcoma incidence ( J:234760 )

• intramuscularly Ad-Cre injected mice develop rhabdomyosarcoma

increased neurofibrosarcoma incidence ( J:234760 )

• mice injected with Ad-Cre in the sciatic nerve develop malignant peripheral nerve sheath tumors in the region at a mean time of 4.1 months after cre exposure

muscle

increased rhabdomyosarcoma incidence ( J:234760 )

• intramuscularly Ad-Cre injected mice develop rhabdomyosarcoma

nervous system

increased neurofibrosarcoma incidence ( J:234760 )

• mice injected with Ad-Cre in the sciatic nerve develop malignant peripheral nerve sheath tumors in the region at a mean time of 4.1 months after cre exposure

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sarcoma		DOID:1115		J:234760

Genotype
MGI:3710235

cn10

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Tg(Mpz-cre)94Imeg/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

growth/size/body

decreased body size ( J:80323 )

respiratory system

respiratory failure ( J:80323 )

• pups do not initiate normal respiration

nervous system

abnormal adrenergic chromaffin cell morphology ( J:80323 )

• increase in the number of adrenal medullary cells, suggesting pheochromocytoma

increased ganglioneuroma incidence ( J:80323 )

increased gangliosarcoma incidence ( J:80323 )

abnormal sympathetic ganglion morphology ( J:80323 )

• massively enlarged sympathetic ganglia that consist of axons that stain for neurofilament and small cell bodies with large nuclei that express tyrosine hydroxylase, a morphology consistent with ganglioneuroma or ganglioneurosarcoma

endocrine/exocrine glands

abnormal adrenal gland morphology ( J:80323 )

abnormal adrenal cortex morphology ( J:80323 )

• a thinning and distortion of the adrenal cortex

thin adrenal cortex ( J:80323 )

abnormal adrenergic chromaffin cell morphology ( J:80323 )

• increase in the number of adrenal medullary cells, suggesting pheochromocytoma

enlarged adrenal glands ( J:80323 )

increased pheochromocytoma incidence ( J:80323 )

neoplasm

increased tumor incidence ( J:80323 )

• develop tumors of neural crest origin such as ganglioneuroma, ganglioneurosarcoma, and pheochromocytoma

increased pheochromocytoma incidence ( J:80323 )

increased ganglioneuroma incidence ( J:80323 )

increased gangliosarcoma incidence ( J:80323 )

cardiovascular system

cardiovascular system phenotype ( J:80323 )

N • normal cardiac development

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:80323

Genotype
MGI:4849442

cn11

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Tg(Gfap-cre)77.6Mvs/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6NHsd

neoplasm

neoplasm ( J:154673 )

N • mutants do not develop tumors

Genotype
MGI:3710237

cn12

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

growth/size/body

decreased body size ( J:80323 )

respiratory system

respiratory failure ( J:80323 )

• pups do not initiate normal respiration

nervous system

abnormal adrenergic chromaffin cell morphology ( J:80323 )

• increase in the number of adrenal medullary cells, suggesting pheochromocytoma

increased ganglioneuroma incidence ( J:80323 )

increased gangliosarcoma incidence ( J:80323 )

abnormal sympathetic ganglion morphology ( J:80323 )

• massively enlarged sympathetic ganglia that consist of axons that stain for neurofilament and small cell bodies with large nuclei that express tyrosine hydroxylase, a morphology consistent with ganglioneuroma or ganglioneurosarcoma

endocrine/exocrine glands

abnormal adrenal gland morphology ( J:80323 )

abnormal adrenal cortex morphology ( J:80323 )

• a thinning and distortion of the adrenal cortex

thin adrenal cortex ( J:80323 )

abnormal adrenergic chromaffin cell morphology ( J:80323 )

• increase in the number of adrenal medullary cells, suggesting pheochromocytoma

enlarged adrenal glands ( J:80323 )

increased pheochromocytoma incidence ( J:80323 )

neoplasm

increased tumor incidence ( J:80323 )

• develop tumors of neural crest origin such as ganglioneuroma, ganglioneurosarcoma, and pheochromocytoma

increased pheochromocytoma incidence ( J:80323 )

increased ganglioneuroma incidence ( J:80323 )

increased gangliosarcoma incidence ( J:80323 )

cardiovascular system

cardiovascular system phenotype ( J:80323 )

N • normal cardiac development

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:80323

Genotype
MGI:2176767

cn13

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Tg(Syn1-cre)671Jxm/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

growth/size/body

decreased body weight ( J:68558 )

• body weight and size are about 50% of normal

postnatal growth retardation ( J:68558 )

• 3-4 days after birth, mice begin to exhibit growth retardation that is sustained into adulthood

nervous system

decreased forebrain size ( J:68558 )

• forebrain, but not the rest of the brain, is reduced in size, however mice exhibit normal neuronal development

abnormal cerebral cortex morphology ( J:68558 )

• increase in cell density in the cerebral cortex, often resulting in less apparent lamination

thin cerebral cortex ( J:68558 )

• about 20% reduction in coritcal thickness

astrocytosis ( J:68558 )

• mice display astrogliosis in various brain regions, however do not develop neuronal degeneration or microgliosis

behavior/neurological

abnormal learning/memory/conditioning ( J:68558 )

• mice display severe learning disability

neoplasm

neoplasm ( J:68558 )

N • no evidence of tumors; optic gliomas, astrocytomas, or neurofibroma are not observed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:68558

Genotype
MGI:5544056

cn14

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

mortality/aging

premature death ( J:90973 )

• 50% of pIpC treated mice die by 7.5 months of age

hematopoietic system

abnormal definitive hematopoiesis ( J:90973 )

• pIpC injected mice at 3 to 5 days of age develop overt signs of myeloproliferative disease beginning between 5 and 6 months of age

• pIpC injected mice show a shift in hematopoiesis from the marrow to the spleen

abnormal common myeloid progenitor cell morphology ( J:90973 )

• myeloid progenitors from pIpC injected mice show increased proliferation

abnormal myelopoiesis ( J:90973 )

• spleen from pIpC injected mice shows a massive increase in myelopoiesis

abnormal bone marrow cell morphology/development ( J:90973 )

• apoptosis is reduced in the bone marrow of pIpC injected mice

• bone marrow from pIpC injected mice is highly cellular, comprised of myeloid cells at various stages of differentiation

• increase in numbers of immature monocytic cells in the bone marrow of pIpC treated mice

• bone marrow from pIpC injected mice contains elevated numbers of CFU-GM and an increase in the numbers of CFU-GM that are hypersensitive to granulocyte-macrophage colony stimulating factor (GM-CSF) and CFU-GM colonies are larger than normal and show abnormal spreading morphology

abnormal hematopoietic cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit elevated numbers of differentiated lymphoid cells by 3 months of age

increased leukocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit elevated leukocyte counts by 3 months of age

• cultures from pIpC injected mice show an increase in the percentage of monocyte-macrophage cells

increased granulocyte number ( J:90973 )

• pIpC injected mice show an increase in numbers of differentiated granulocytic cells

increased neutrophil cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal neutrophils by 3 months of age

increased lymphocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal lymphocytes by 3 months of age

increased monocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal monocytes by 3 months of age

• pIpC injected mice show an increase in numbers of immature monocytic cells in the bone marrow

abnormal myeloid leukocyte morphology ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit elevated numbers of differentiated myeloid cells by 3 months of age

abnormal spleen morphology ( J:90973 )

• spleens from pIpC injected mice contain large numbers of CFU-GM

enlarged spleen ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit progressive splenomegaly with extensive infiltration of myeloid cells at various stages of maturation

behavior/neurological

hunched posture ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit abnormal gait by 5-6 months of age

abnormal gait ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit hunching by 5-6 months of age

immune system

abnormal myelopoiesis ( J:90973 )

• spleen from pIpC injected mice shows a massive increase in myelopoiesis

increased leukocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit elevated leukocyte counts by 3 months of age

• cultures from pIpC injected mice show an increase in the percentage of monocyte-macrophage cells

increased lymphocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal lymphocytes by 3 months of age

abnormal myeloid leukocyte morphology ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit elevated numbers of differentiated myeloid cells by 3 months of age

increased granulocyte number ( J:90973 )

• pIpC injected mice show an increase in numbers of differentiated granulocytic cells

increased neutrophil cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal neutrophils by 3 months of age

increased monocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal monocytes by 3 months of age

• pIpC injected mice show an increase in numbers of immature monocytic cells in the bone marrow

abnormal spleen morphology ( J:90973 )

• spleens from pIpC injected mice contain large numbers of CFU-GM

enlarged spleen ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit progressive splenomegaly with extensive infiltration of myeloid cells at various stages of maturation

integument

disheveled coat ( J:90973 )

• pIpC injected mice at 3 to 5 days of age have a disheveled appearance by 5-6 months of age

growth/size/body

enlarged spleen ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit progressive splenomegaly with extensive infiltration of myeloid cells at various stages of maturation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
juvenile myelomonocytic leukemia		DOID:0050458	OMIM:607785	J:90973

Genotype
MGI:3810648

cn15

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Tg(Fabp7-cre,-lacZ)3Gtm/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

mortality/aging

premature death ( J:139866 )

• no mice survive beyond 3 months of age

postnatal lethality, incomplete penetrance ( J:139866 )

• the majority of pups fail to survive to weaning

• median survival is 18 days

nervous system

nervous system phenotype ( J:139866 )

N • brain weight is not significantly decreased and the major anatomical areas of the forebrain are not significantly different from controls

abnormal pituitary gland morphology ( J:138868 )

small adenohypophysis ( J:138868 )

• significantly smaller than control littermates

• however, the posterior lobe is similar in size to that in controls

abnormal pituitary gland development ( J:138868 )

• 3-fold reduction in proliferating cells in the anterior lobe of the pituitary gland

• no change in proliferation in the posterior lobe

small pituitary gland ( J:138868 )

abnormal brain development ( J:139866 )

• increases in the numbers of Olig2+ glial and BLBP+ neuroglial progenitors are seen throughout the brain

• expression analysis indicates abnormalities in development and differentiation of neocortical neurons

abnormal hippocampus morphology ( J:139866 )

• at 1 week of age, an increase in proliferating cells is seen in the CA2/3 region

• however, when normalized to the number of progenitor cellsno increase in the percentage of proliferating cells is detected

abnormal secondary somatosensory cortex morphology ( J:139866 )

• decrease in the distance between the corpus callosum and the brain surface in the secondary somatosensory cortex indicating a reduction in cortex thickness

• pre- and post-natal treatment with Rolipram restores normal somatosensory cortical thickness

abnormal CNS glial cell morphology ( J:139866 )

• increase in the number of NG2+ glial cells in the brain including the somatosensory cortex

abnormal astrocyte morphology ( J:139866 )

• increase in the number of GFAP+ astrocytes in the brain

• gene-dose dependent increase in the number of astrocytes in the CA1 region of the hippocampus

increased oligodendrocyte number ( J:139866 )

• increase in the number of APC+ oligodendroglial cells in the brain including the fimbria

abnormal dendrite morphology ( J:139866 )

• apical dendrites of layer II/III pyramidal neurons in the somatosensory cortex are shorter compared to littermate controls

• pre- and post-natal treatment with Rolipram partially restores neurite length

abnormal nervous system physiology ( J:139866 )

• decrease in intracellular cAMP levels in the brain

abnormal neuronal precursor proliferation ( J:139866 )

• increase in proliferation at E13.5 and to a lesser extent at E17.5 primarily in neuroglial progenitor cells

abnormal pituitary gland physiology ( J:138868 )

• significant reduction in growth hormone and prolactin mRNA levels

abnormal hypothalamus physiology ( J:138868 )

• 50% reduction in cAMP levels in hypothalamic homogenates

growth/size/body

decreased body weight ( J:138868 , J:139866 )

• greater than 60% reduction in body weight compared to controls by 3 weeks of age (J:138868)

• weigh about 30% of the weight of control littermates at 2 - 3 months of age (J:138868)

• Rolipram treatment increases body weight but mice are still smaller than controls (J:138868)

• at P18, weight is less than 50% that of control littermates (J:139866)

postnatal growth retardation ( J:138868 , J:139866 )

• severe growth retardation develops during the first week after birth (J:138868)

• develop progressive growth retardation from P3 (J:139866)

• all major organ systems, except the central nervous system, display growth retardation at P18 (J:139866)

endocrine/exocrine glands

abnormal pituitary gland morphology ( J:138868 )

small adenohypophysis ( J:138868 )

• significantly smaller than control littermates

• however, the posterior lobe is similar in size to that in controls

abnormal pituitary gland development ( J:138868 )

• 3-fold reduction in proliferating cells in the anterior lobe of the pituitary gland

• no change in proliferation in the posterior lobe

small pituitary gland ( J:138868 )

abnormal pituitary gland physiology ( J:138868 )

• significant reduction in growth hormone and prolactin mRNA levels

homeostasis/metabolism

abnormal hormone level ( J:138868 )

• decrease in growth hormone releasing hormone levels in the primary capillaries of the hypophyseal portal system

decreased circulating growth hormone level ( J:138868 )

• a 65% reduction in liver Igf1 mRNA levels indicates a reduction in circulating growth hormone levels

behavior/neurological

abnormal behavior ( J:139866 )

• extreme sensitivity to handling

abnormal voluntary movement ( J:139866 )

• limited range of movement of the hindlimbs

cellular

abnormal neuronal precursor proliferation ( J:139866 )

• increase in proliferation at E13.5 and to a lesser extent at E17.5 primarily in neuroglial progenitor cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:138868

Genotype
MGI:3810649

cn16

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Tg(Fabp7-cre,-lacZ)3Gtm/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

nervous system

abnormal astrocyte morphology ( J:139866 )

• gene-dose dependent increase in the number of astrocytes in the CA1 region of the hippocampus

Genotype
MGI:3810651

cn17

• Allelic Composition: Gt(ROSA)26Sor^tm1Fia/Gt(ROSA)26Sor⁺; Nf1^tm1Par/Nf1^tm1Par; Tg(Fabp7-cre,-lacZ)3Gtm/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

nervous system

small adenohypophysis ( J:138868 )

• significantly smaller than control littermates

growth/size/body

decreased body weight ( J:138868 )

endocrine/exocrine glands

small adenohypophysis ( J:138868 )

• significantly smaller than control littermates

homeostasis/metabolism

decreased circulating growth hormone level ( J:138868 )

• reduction in liver Igf1 mRNA levels indicates a reduction in circulating growth hormone levels

Genotype
MGI:5493228

cn18

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * C57BL/6N * SJL/J

skeleton

increased osteoclast cell number ( J:193350 )

• callus following fracture shows increased number of osteoclasts; most osteoclasts are localized within fibrous tissue and not on the bone surface as in controls

abnormal bone healing ( J:193350 )

• mutants exhibit delayed and defective fracture healing characterized by diminished cartilaginous callus formation, increased bone formation near the cortical bone on the periosteum but not in the fracture gap, and persistence of cartilage at day 21 such that bony bridging is not observed

• while total callus volume following fracture is larger in mutants at day 7 and 10 due to rapid initial growth of fibrous tissue (desmal type ossification), by day 14 and 21, the total callus volume is significantly smaller

• accumulation and persistence of fibrous tissue in the fracture gap, with increased numbers of osteoclasts

• increase in number of blood vessels in mutant fractures (in callus) compared to controls, indicating increased vascularization of the fracture tissue, however no osteogenesis results from this increased vascularization

• ectopic fat tissue is seen in the fracture site

decreased bone mineral density ( J:193350 )

• decrease of regenerative tissue bone mineral density following fracture

increased compact bone volume ( J:193350 )

• dramatic cortical bone thickening following fracture

abnormal osteoblast cell number ( J:193350 )

• fewer osteoblasts are seen within the fracture gap throughout healing compared to controls, however, osteoblast number is increased at the periosteal surface

abnormal cartilage morphology ( J:193350 )

• bone fractures exhibit impaired cartilage formation and increased periosteal ossification at the cortices

abnormal osteoid morphology ( J:193350 )

• presence of large areas of non-mineralized osteoid in the fracture gap, indicating decreased mineralization of the extracellular matrix

increased osteoid thickness ( J:193350 )

• thickening of the osteoid layer in the periosteal region following fracture

abnormal endochondral bone ossification ( J:193350 )

• endochondrial formation is impaired following fracture but periosteal bone formation is enhanced

fragile skeleton ( J:193350 )

• bones are weaker; femora show lower torsional stiffness and ultimate torque at failure compared to controls

• fractured bones of mutants that are allowed to heal also exhibit a lower torsional stiffness and ultimate torque at failure compared to controls

homeostasis/metabolism

abnormal bone healing ( J:193350 )

• mutants exhibit delayed and defective fracture healing characterized by diminished cartilaginous callus formation, increased bone formation near the cortical bone on the periosteum but not in the fracture gap, and persistence of cartilage at day 21 such that bony bridging is not observed

• while total callus volume following fracture is larger in mutants at day 7 and 10 due to rapid initial growth of fibrous tissue (desmal type ossification), by day 14 and 21, the total callus volume is significantly smaller

• accumulation and persistence of fibrous tissue in the fracture gap, with increased numbers of osteoclasts

• increase in number of blood vessels in mutant fractures (in callus) compared to controls, indicating increased vascularization of the fracture tissue, however no osteogenesis results from this increased vascularization

• ectopic fat tissue is seen in the fracture site

hematopoietic system

increased osteoclast cell number ( J:193350 )

• callus following fracture shows increased number of osteoclasts; most osteoclasts are localized within fibrous tissue and not on the bone surface as in controls

immune system

increased osteoclast cell number ( J:193350 )

• callus following fracture shows increased number of osteoclasts; most osteoclasts are localized within fibrous tissue and not on the bone surface as in controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:193350

Genotype
MGI:5492109

cn19

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J

growth/size/body

decreased body weight ( J:173779 )

• weight is on average reduced by 25%

limbs/digits/tail

short limbs ( J:173779 )

• short-limbed dwarfism, with mutants showing a reduction in entire limb size

muscle

abnormal muscle morphology ( J:173779 )

• mutants exhibit muscle dystrophy

• large areas of dystrophic musculature are occupied by fat tissue

• muscle connective tissue shows increased proliferation at E14.5 and an increase in connective tissue in muscles is already seen at E16.5

• muscle fibers are thinned out at E16.5

abnormal muscle development ( J:173779 )

• marker analysis indicates a defect in muscle formation at E13.5, with specific muscle primordial reduced in size or entirely missing; approximate 30% reduction in the m. triceps size and about 50% reduction in the m. gluteus maximus size of E13.5 embryos

• the m. latissimus dorsi appears smaller and shows rarefaction of muscle fibers

• distal muscle groups in the extremities are most affected, with some muscles completely missing, indicating that the muscle differentiation process is disturbed

abnormal myogenesis ( J:173779 )

• defect in myogenesis affecting the terminal differentiation of myoblasts between E12.5 and E14.5

abnormal myoblast differentiation ( J:173779 )

• maker analysis indicates a severe disruption of myoblast terminal differentiation

increased myoblast proliferation ( J:173779 )

• marker analysis indicates that migration and proliferation of pre-muscle cells at E11.5 are normal but increased proliferation of myoblasts in ventral muscle masses is seen

abnormal muscle fiber morphology ( J:173779 )

• muscles show a 20% increase in the number of fibers with cleft-like invaginations (split fibers)

• muscle fiber size appears more variable than in controls, however no overt muscle regeneration is seen

decreased skeletal muscle fiber number ( J:173779 )

• total number of muscle fibers is reduced by 50% in the triceps

decreased muscle weight ( J:173779 )

• weight of triceps muscle is reduced by more than 50%

decreased skeletal muscle mass ( J:173779 )

• reduction in muscle size and mass

skeletal muscle fibrosis ( J:173779 )

• generalized muscle fibrosis, characterized by expansion of collagen-rich connective tissue, and reduction in total number of muscle fibers

abnormal muscle physiology ( J:173779 )

• in the force gauge pull test, mice show a dramatic reduction in muscle force

• satellite cells exhibit normal self-renewal but impaired differentiation as indicated by diminished myotube formatio

cellular

abnormal myoblast differentiation ( J:173779 )

• maker analysis indicates a severe disruption of myoblast terminal differentiation

increased myoblast proliferation ( J:173779 )

• marker analysis indicates that migration and proliferation of pre-muscle cells at E11.5 are normal but increased proliferation of myoblasts in ventral muscle masses is seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:173779

Genotype
MGI:3710236

cn20

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Tg(Pax3-cre)1Joe/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

growth/size/body

decreased body size ( J:80323 )

respiratory system

respiratory failure ( J:80323 )

• pups do not initiate normal respiration

nervous system

abnormal adrenergic chromaffin cell morphology ( J:80323 )

• increase in the number of adrenal medullary cells, suggesting pheochromocytoma

increased ganglioneuroma incidence ( J:80323 )

increased gangliosarcoma incidence ( J:80323 )

abnormal sympathetic ganglion morphology ( J:80323 )

• massively enlarged sympathetic ganglia that consist of axons that stain for neurofilament and small cell bodies with large nuclei that express tyrosine hydroxylase, a morphology consistent with ganglioneuroma or ganglioneurosarcoma

endocrine/exocrine glands

abnormal adrenal gland morphology ( J:80323 )

abnormal adrenal cortex morphology ( J:80323 )

• a thinning and distortion of the adrenal cortex

thin adrenal cortex ( J:80323 )

abnormal adrenergic chromaffin cell morphology ( J:80323 )

• increase in the number of adrenal medullary cells, suggesting pheochromocytoma

enlarged adrenal glands ( J:80323 )

increased pheochromocytoma incidence ( J:80323 )

neoplasm

increased tumor incidence ( J:80323 )

• develop tumors of neural crest origin such as ganglioneuroma, ganglioneurosarcoma, and pheochromocytoma

increased pheochromocytoma incidence ( J:80323 )

increased ganglioneuroma incidence ( J:80323 )

increased gangliosarcoma incidence ( J:80323 )

cardiovascular system

cardiovascular system phenotype ( J:80323 )

N • normal cardiac development

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:80323

Genotype
MGI:3710234

cn21

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

cardiovascular system

thin myocardium compact layer ( J:80323 )

thin myocardium ( J:80323 )

• 8 of 11 embryos exhibit a thinned myocardium

increased atrioventricular cushion size ( J:80323 )

• 8 of 11 embryos show an enlarged atrioventricular cushion

double outlet right ventricle ( J:80323 )

• seen in 8 of 11 embryos

ventricular septal defect ( J:80323 )

• 10 of 11 embryos exhibit ventricular septal defects

pericardial effusion ( J:80323 )

homeostasis/metabolism

pericardial effusion ( J:80323 )

muscle

thin myocardium compact layer ( J:80323 )

thin myocardium ( J:80323 )

• 8 of 11 embryos exhibit a thinned myocardium

Genotype
MGI:3689705

cn22

• 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

cn23

• 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

cn24

• 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

cn25

• 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:3776056

cn26

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Tyj; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

embryo

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
MGI:3776064

cn27

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Tyj; Tg(Mpz-cre)1Brn/0
• Genetic Background: involves: 129/Sv * FVB/N

nervous system

nervous system phenotype ( J:131914 )

N • neural crest stem cells do not abnormally persist in the peripheral nervous system in adult mice

increased neurofibroma incidence ( J:131914 )

• at 15 - 20 months of age, all 6 mice examined had plexiform neurofibromas compared to 0 fibromas in control littermates

neoplasm

increased neurofibroma incidence ( J:131914 )

• at 15 - 20 months of age, all 6 mice examined had plexiform neurofibromas compared to 0 fibromas in control littermates

Genotype
MGI:5301658

cx28

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Rnf7^Gt(XE423)Byg/Rnf7^Gt(XE423)Byg
• Genetic Background: involves: 129 * C57BL/6

cellular

increased apoptosis ( J:178926 )

• partial rescue of apoptosis in the spinal cord compared to mice null for Rnf7 alone

• rescue of neuronal apoptosis compared to mice null for Rnf7 alone

decreased cell proliferation ( J:178926 )

• decrease in proliferation of neuronal precursor cells in the neocortex

cardiovascular system

abnormal angiogenesis ( J:178926 )

• partial restoration of angiogenesis in the head compared to mice null for Rnf7 alone

embryo

embryonic growth retardation ( J:178926 )

growth/size/body

embryonic growth retardation ( J:178926 )