Phenotypes associated with this allele

• Allele Symbol: Nf2^tm2Gth
• Allele Name: targeted mutation 2, Gilles Thomas
• Allele ID: MGI:1926955
• Summary: 40 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Nf2^tm2Gth/Nf2^tm2Gth	involves: 129P2/OlaHsd	MGI:3850450
cn2	Nf2^tm2Gth/Nf2^tm2Gth	involves: 129P2/OlaHsd * FVB/N	MGI:5051645
cn3	Cdkn2a^tm2Brn/Cdkn2a^tm2Brn Nf2^tm2Gth/Nf2^tm2Gth	involves: 129P2/OlaHsd	MGI:3850440
cn4	Nf2^tm2Gth/Nf2^tm2Gth Tg(rx3-icre)1Mjam/0	involves: 129P2/OlaHsd	MGI:7261162
cn5	Nf2^tm2Gth/Nf2^tm2Gth Yap1^tm2.1Dupa/Yap1^tm2.1Dupa	involves: 129P2/OlaHsd	MGI:5660339
cn6	Cdkn2a^tm2Brn/Cdkn2a^+ Nf2^tm2Gth/Nf2^tm2Gth	involves: 129P2/OlaHsd	MGI:3850445
cn7	Cdkn2a^tm2Brn/Cdkn2a^tm2Brn Nf2^tm2Gth/Nf2^+	involves: 129P2/OlaHsd	MGI:3850444
cn8	Hras^tm1Jaf/Hras^tm1Jaf Nf2^tm2Gth/Nf2^tm2Gth Tg(TPO-cre)1Shk/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * FVB/NCr	MGI:5784770
cn9	Nf2^tm2Gth/Nf2^tm2Gth Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:3850443
cn10	Cdkn2a^tm1.1Brn/Cdkn2a^tm1.1Brn Nf2^tm2Gth/Nf2^tm2Gth Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:3850439
cn11	Nf2^tm2Gth/Nf2^+ Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:3850446
cn12	Nf2^tm2Gth/Nf2^tm2Gth Trp53^tm1Brn/Trp53^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:3850447
cn13	Cdkn2a^tm1.1Brn/Cdkn2a^+ Nf2^tm2Gth/Nf2^tm2Gth Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:3850449
cn14	Nf2^tm2Gth/Nf2^tm2Gth Trp53^tm1Brd/Trp53^+ Tg(Mpz-cre)3Brn/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N	MGI:3850409
cn15	Nf2^tm2Gth/Nf2^tm2Gth Trp53^tm1Brd/Trp53^+ Tg(Mpz-cre)2Brn/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N	MGI:3850407
cn16	Nf2^tm2Gth/Nf2^+ Trp53^tm1Brd/Trp53^+ Tg(Mpz-cre)3Brn/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N	MGI:3850410
cn17	Nf2^tm2Gth/Nf2^tm2Gth Trp53^tm1Brd/Trp53^tm1Brd Tg(Mpz-cre)2Brn/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N	MGI:3850408
cn18	Nf2^tm2Gth/Nf2^tm2Gth Tg(Mx1-cre)1Cgn/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3850479
cn19	Nf2^tm2Gth/Nf2^tm2Gth Yap1^tm1.1Dupa/Yap1^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:4819843
cn20	Nf2^tm2Gth/Nf2^tm2Gth Yap1^tm1.1Dupa/Yap1^tm1.1Dupa Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:4819842
cn21	Nf2^tm2Gth/Nf2^tm2Gth Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:4819845
cn22	Nf2^tm2Gth/Nf2^tm2Gth Tg(Vil1-cre)20Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:3850478
cn23	Nf2^tm2Gth/Nf2^tm2Gth Tg(Nes-cre)1Kln/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:4819847
cn24	Nf2^tm2Gth/Nf2^tm2Gth Tg(Mpz-cre)4Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3850391
cn25	Cdkn2a^tm1.1Brn/Cdkn2a^tm1.1Brn Nf2^tm2Gth/Nf2^tm2Gth	involves: 129P2/OlaHsd * FVB/N	MGI:3850412
cn26	Nf2^tm2Gth/Nf2^tm2Gth Tg(Mpz-cre)1Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3850388
cn27	Nf2^tm2Gth/Nf2^+ Tg(Mpz-cre)#Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3850405
cn28	Nf2^tm1Gth/Nf2^tm2Gth Tg(Mpz-cre)#Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3850403
cn29	Nf2^tm2Gth/Nf2^tm2Gth Tg(Mpz-cre)3Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3850390
cn30	Nf2^tm2Gth/Nf2^tm2Gth Tg(Mpz-cre)2Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3850389
cn31	Nf2^tm1Gth/Nf2^tm2Gth Tg(Mpz-cre)4Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3850402
cn32	Nf2^tm2Gth/Nf2^tm2Gth Ptgds^tm1.1(cre)Gvn/Ptgds^+	involves: 129P2/OlaHsd * FVB/N	MGI:5051641
cn33	Cdkn2a^tm1.1Brn/Cdkn2a^tm1.1Brn Nf2^tm2Gth/Nf2^tm2Gth Ptgds^tm1.1(cre)Gvn/Ptgds^+	involves: 129P2/OlaHsd * FVB/N	MGI:5051643
cn34	Nf2^tm2Gth/Nf2^tm2Gth Ptgds^tm1.1(cre)Gvn/Ptgds^+ Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd * FVB/N	MGI:5051644
cn35	Nf2^tm1Gth/Nf2^tm2Gth Tg(Mpz-cre)3Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3850395
cn36	Nf2^tm1Gth/Nf2^tm2Gth Tg(Mpz-cre)2Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3850394
cn37	Nf2^tm1Gth/Nf2^tm2Gth Tg(Mpz-cre)1Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3850393
cn38	Nf2^tm2Gth/Nf2^tm2Gth Tg(Mpz-cre)#Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3850392
cn39	Nf2^tm2Gth/Nf2^tm2Gth Tg(TPO-cre)1Shk/0	involves: 129P2/OlaHsd * FVB/NCr	MGI:5784767
cn40	Nf2^tm2Gth/Nf2^tm2Gth Tg(Postn-cre)1Sjc/0	involves: 129P2/OlaHsd * FVB/NTac	MGI:5619302

Genotype
MGI:3850450

cn1

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth
• Genetic Background: involves: 129P2/OlaHsd

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

neoplasm

increased tumor incidence ( J:132943 )

• following adenoviral cre treatment, 5 of 30 mice develop malignant mesotheliomas-like thoracic tumors

• following adenoviral cre treatment, mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

endocrine/exocrine glands

abnormal bile duct epithelium morphology ( J:223215 )

• mice develop mild focal proliferation of cryokeratin-positive biliary epithelial cells 2 months following Ad-Cre injection

liver/biliary system

abnormal bile duct epithelium morphology ( J:223215 )

• mice develop mild focal proliferation of cryokeratin-positive biliary epithelial cells 2 months following Ad-Cre injection

enlarged liver ( J:132943 )

• following adenoviral cre treatment, mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

growth/size/body

enlarged liver ( J:132943 )

• following adenoviral cre treatment, mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

Genotype
MGI:5051645

cn2

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

neoplasm

increased meningioma incidence ( J:173718 )

• later postnatal inactivation of Nf2 in arachnoidal cells by injection of adenoviral cre into the cerebro-spinal fluid of 10 day-old pups or adult mice does not result in meningioma formation, in contrast to embryonic Nf2 deletion or previous data for inactivation in 1-2 day-old mice

nervous system

increased meningioma incidence ( J:173718 )

• later postnatal inactivation of Nf2 in arachnoidal cells by injection of adenoviral cre into the cerebro-spinal fluid of 10 day-old pups or adult mice does not result in meningioma formation, in contrast to embryonic Nf2 deletion or previous data for inactivation in 1-2 day-old mice

Genotype
MGI:3850440

cn3

• Allelic Composition: Cdkn2a^tm2Brn/Cdkn2a^tm2Brn; Nf2^tm2Gth/Nf2^tm2Gth
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

premature death ( J:132943 )

• following adenoviral cre treatment, median survival time is 220 days

neoplasm

increased tumor incidence ( J:132943 )

• following adenoviral cre treatment, 83% of mice develop highly invasive thoracic tumors (including malignant mesotheliomas, 45 of 57; rhabdomyosarcomas, 3 of 57; and schwannomas, 1 of 57)

• following adenoviral cre treatment, mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

• following adenoviral cre treatment, 4% of mice develop aspecific tumors not induced by adeno-cre treatment

• following adenoviral cre treatment, 70% of mice develop aggressive malignant mesotheliomas, which is higher than in mice carrying other combinations of Cdkn2a^tm2Brn, Nf2^tm2Gth, and Trp53^tm1Brn alleles

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 4% of mice following adenoviral cre treatment

increased rhabdomyosarcoma incidence ( J:132943 )

increased leukemia incidence ( J:132943 )

• following adenoviral cre treatment, 7% mice develop monocytic myeloid leukemias

liver/biliary system

enlarged liver ( J:132943 )

• following adenoviral cre treatment, 42% of mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

reproductive system

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 4% of mice following adenoviral cre treatment

muscle

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 4% of mice following adenoviral cre treatment

increased rhabdomyosarcoma incidence ( J:132943 )

growth/size/body

enlarged liver ( J:132943 )

• following adenoviral cre treatment, 42% of mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant mesothelioma		DOID:1790	OMIM:156240	J:132943

Genotype
MGI:7261162

cn4

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(rx3-icre)1Mjam/0
• Genetic Background: involves: 129P2/OlaHsd

vision/eye

retina pigment epithelium hyperplasia ( J:322987 )

• in all subdivisions of the ventral optic cup

failure of eyelid fusion ( J:322987 )

abnormal optic cup morphology ( J:322987 )

• increased cell numbers in the ventral optic cup

• ectopic retinal pigment epithelium in the dorsal optic cup

abnormal optic fissure morphology ( J:322987 )

• with less advanced alignment of margins and increased cellular height particularly in the temporal optic fissure

coloboma ( J:322987 )

• failure of optic fissure fusion during the final process of closing persisting into later stages

abnormal eye physiology ( J:322987 )

• increased ventral retinal pigmented epithelium proliferation

craniofacial

cleft upper lip ( J:322987 )

cleft palate ( J:322987 )

growth/size/body

cleft upper lip ( J:322987 )

cleft palate ( J:322987 )

digestive/alimentary system

cleft palate ( J:322987 )

pigmentation

retina pigment epithelium hyperplasia ( J:322987 )

• in all subdivisions of the ventral optic cup

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
coloboma		DOID:12270	OMIM:120200 OMIM:120300 OMIM:216820	J:322987

Genotype
MGI:5660339

cn5

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Yap1^tm2.1Dupa/Yap1^tm2.1Dupa
• Genetic Background: involves: 129P2/OlaHsd

endocrine/exocrine glands

abnormal bile duct epithelium morphology ( J:223215 )

• extensive proliferation of cryokeratin-positive biliary epithelial cells observed in liver 2 months after adenovirus expressing Cre recombinase (Ad-Cre) injection (Ad-Cre) injection

liver/biliary system

abnormal bile duct epithelium morphology ( J:223215 )

• extensive proliferation of cryokeratin-positive biliary epithelial cells observed in liver 2 months after adenovirus expressing Cre recombinase (Ad-Cre) injection (Ad-Cre) injection

enlarged liver ( J:223215 )

• mice exhibit an enlarged liver 2 months after Ad-Cre injection

abnormal bile duct physiology ( J:223215 )

• mice develop massive bile duct hamarotomas 2 months after Ad-Cre injection as compared to contro

neoplasm

increased hamartoma incidence ( J:223215 )

• mice develop massive bile duct hamarotomas 2 months after Ad-Cre injection as compared to controls

growth/size/body

enlarged liver ( J:223215 )

• mice exhibit an enlarged liver 2 months after Ad-Cre injection

Genotype
MGI:3850445

cn6

• Allelic Composition: Cdkn2a^tm2Brn/Cdkn2a⁺; Nf2^tm2Gth/Nf2^tm2Gth
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

premature death ( J:132943 )

• following adenoviral cre treatment, median survival time is 495 days

neoplasm

increased tumor incidence ( J:132943 )

• following adenoviral cre treatment, 35% of mice develop thoracic tumors (including malignant mesotheliomas, 18 of 52) with a longer latency than in mice homozygous for all alleles

• following adenoviral cre treatment, mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

• following adenoviral cre treatment, 19% of mice develop aspecific tumors not induced by adeno-cre treatment

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 16% of mice following adenoviral cre treatment

increased leukemia incidence ( J:132943 )

• following adenoviral cre treatment, 16% of mice develop monocytic myeloid leukemias

liver/biliary system

enlarged liver ( J:132943 )

• following adenoviral cre treatment, mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

muscle

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 16% of mice following adenoviral cre treatment

growth/size/body

enlarged liver ( J:132943 )

• following adenoviral cre treatment, mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

reproductive system

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 16% of mice following adenoviral cre treatment

Genotype
MGI:3850444

cn7

• Allelic Composition: Cdkn2a^tm2Brn/Cdkn2a^tm2Brn; Nf2^tm2Gth/Nf2⁺
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

premature death ( J:132943 )

• following adenoviral cre treatment, median survival time is 410 days

neoplasm

increased tumor incidence ( J:132943 )

• following adenoviral cre treatment, 34% of mice develop thoracic tumors (including malignant mesotheliomas, 14 of 41) with a longer latency than in mice homozygous for all alleles

• following adenoviral cre treatment, 24% of mice develop aspecific tumors not induced by adeno-cre treatment

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 17% of mice following adenoviral cre treatment

increased leukemia incidence ( J:132943 )

• following adenoviral cre treatment, 54% of mice develop monocytic myeloid leukemias

muscle

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 17% of mice following adenoviral cre treatment

reproductive system

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 17% of mice following adenoviral cre treatment

Genotype
MGI:5784770

cn8

• Allelic Composition: Hras^tm1Jaf/Hras^tm1Jaf; Nf2^tm2Gth/Nf2^tm2Gth; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * FVB/NCr

endocrine/exocrine glands

increased thyroid tumor incidence ( J:231492 )

• mice develop large thyroid cancers with high penetrance, with most being poorly differentiated thyroid cancer

• treatment with AZD6244 results in a reduction of tumor size

neoplasm

increased thyroid tumor incidence ( J:231492 )

• mice develop large thyroid cancers with high penetrance, with most being poorly differentiated thyroid cancer

• treatment with AZD6244 results in a reduction of tumor size

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid cancer		DOID:1781		J:231492

Genotype
MGI:3850443

cn9

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

mortality/aging

premature death ( J:132943 )

• following adenoviral cre treatment, median survival time is 135 days

neoplasm

increased tumor incidence ( J:132943 )

• following adenoviral cre treatment, 86% of mice develop thoracic tumors (including malignant mesotheliomas, 45 of 55; rhabdomyosarcomas, 2 of 55; and schwannomas, 1 of 55)

• following adenoviral cre treatment, mice develop either non-aggressive epitheloid or mixed tumors with confined invasion of the visceral pleural or (sarcomatoid) tumors with strong invasion of visceral and parietal pleura

• following adenoviral cre treatment, 4% of mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

• following adenoviral cre treatment, 11% of mice develop aspecific tumors not induced by adeno-cre treatment

• following adenoviral cre treatment, latency to developing malignant mesotheliomas is lower than in mice carrying other combinations of Cdkn2a^tm2Brn, Nf2^tm2Gth, and Trp53^tm1Brn alleles

increased T cell derived lymphoma incidence ( J:132943 )

• a few following adenoviral cre treatment

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 7% of mice following adenoviral cre treatment

increased rhabdomyosarcoma incidence ( J:132943 )

increased leukemia incidence ( J:132943 )

• following adenoviral cre treatment, 7% mice develop monocytic myeloid leukemias

increased mesothelioma incidence ( J:132943 )

• following adenoviral cre treatment, latency to developing malignant mesotheliomas is lower than in mice carrying other combinations of Cdkn2a^tm2Brn, Nf2^tm2Gth, and Trp53^tm1Brn alleles

increased Schwannoma incidence ( J:132943 )

liver/biliary system

enlarged liver ( J:132943 )

• following adenoviral cre treatment, 4% of mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

muscle

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 7% of mice following adenoviral cre treatment

increased rhabdomyosarcoma incidence ( J:132943 )

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:132943 )

• a few following adenoviral cre treatment

growth/size/body

enlarged liver ( J:132943 )

• following adenoviral cre treatment, 4% of mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

reproductive system

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 7% of mice following adenoviral cre treatment

nervous system

increased Schwannoma incidence ( J:132943 )

immune system

increased T cell derived lymphoma incidence ( J:132943 )

• a few following adenoviral cre treatment

hematopoietic system

increased T cell derived lymphoma incidence ( J:132943 )

• a few following adenoviral cre treatment

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant mesothelioma		DOID:1790	OMIM:156240	J:132943

Genotype
MGI:3850439

cn10

• Allelic Composition: Cdkn2a^tm1.1Brn/Cdkn2a^tm1.1Brn; Nf2^tm2Gth/Nf2^tm2Gth; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

mortality/aging

premature death ( J:132943 )

• following adenoviral cre treatment, median survival time is 80 days

neoplasm

increased tumor incidence ( J:132943 )

• following adenoviral cre treatment, 100% of mice develop highly invasive thoracic tumors (including malignant mesotheliomas, 47 of 51; rhabdomyosarcomas, 4 of 51; and schwannomas, 1 of 51)

• following adenoviral cre treatment, 75% of mice develop of aggressive malignant mesotheliomas at a shorter latency than in mice carrying other combinations of Cdkn2a^tm2Brn, Nf2^tm2Gth, and Trp53^tm1Brn alleles

increased rhabdomyosarcoma incidence ( J:132943 )

increased mesothelioma incidence ( J:132943 )

• following adenoviral cre treatment, 75% of mice develop of aggressive malignant mesotheliomas at a shorter latency than in mice carrying other combinations of Cdkn2a^tm2Brn, Nf2^tm2Gth, and Trp53^tm1Brn alleles

increased Schwannoma incidence ( J:132943 )

nervous system

increased Schwannoma incidence ( J:132943 )

muscle

increased rhabdomyosarcoma incidence ( J:132943 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant mesothelioma		DOID:1790	OMIM:156240	J:132943

Genotype
MGI:3850446

cn11

• Allelic Composition: Nf2^tm2Gth/Nf2⁺; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

mortality/aging

premature death ( J:132943 )

• following adenoviral cre treatment, median survival time is 215 days

neoplasm

increased tumor incidence ( J:132943 )

• following adenoviral cre treatment, 62% of mice develop thoracic tumors (including malignant mesothelimas, 20 of 34; and schwannomas, 1 of 34) with a longer latency than in mice homozygous for all alleles

• following adenoviral cre treatment, 21% of mice develop aspecific tumors not induced by adeno-cre treatment

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 9% of mice following adenoviral cre treatment

increased leukemia incidence ( J:132943 )

• following adenoviral cre treatment, 9% of mice develop monocytic myeloid leukemias

increased mesothelioma incidence ( J:132943 )

increased Schwannoma incidence ( J:132943 )

reproductive system

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 9% of mice following adenoviral cre treatment

muscle

increased uterus leiomyoma incidence ( J:132943 )

♀ • in 9% of mice following adenoviral cre treatment

nervous system

increased Schwannoma incidence ( J:132943 )

Genotype
MGI:3850447

cn12

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Trp53^tm1Brn/Trp53⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

mortality/aging

premature death ( J:132943 )

neoplasm

increased tumor incidence ( J:132943 )

• following adenoviral cre treatment, 40% of mice develop thoracic tumors (including malignant mesotheliomas, 5 of 20; and schwannomas, 3 of 20) with a longer latency than in mice homozygous for all alleles

• following adenoviral cre treatment, one mouse developed hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

• following adenoviral cre treatment, 2% of mice develop aspecific tumors not induced by adeno-cre treatment

increased uterus leiomyoma incidence ( J:132943 )

♀

increased leukemia incidence ( J:132943 )

increased mesothelioma incidence ( J:132943 )

increased Schwannoma incidence ( J:132943 )

liver/biliary system

enlarged liver ( J:132943 )

• following adenoviral cre treatment, 1 mouse developed hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

reproductive system

increased uterus leiomyoma incidence ( J:132943 )

♀

growth/size/body

enlarged liver ( J:132943 )

• following adenoviral cre treatment, 1 mouse developed hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus

nervous system

increased Schwannoma incidence ( J:132943 )

muscle

increased uterus leiomyoma incidence ( J:132943 )

♀

Genotype
MGI:3850449

cn13

• Allelic Composition: Cdkn2a^tm1.1Brn/Cdkn2a⁺; Nf2^tm2Gth/Nf2^tm2Gth; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

neoplasm

increased metastatic potential ( J:132943 )

• following adenoviral cre treatment, the parietal pleura often shows invasion with concomitant pleural effusion

increased tumor incidence ( J:132943 )

• following adenoviral cre treatment, 94% of mice develop aggressive thoracic tumors (including malignant mesotheliomas, 15 of 51; and rhabdomyosarcomas, 1 of 51) with the parietal pleura often showing invasion with concomitant pleural effusion

• following adenoviral cre treatment, 1% of mice develop aspecific tumors not induced by adeno-cre treatment

increased rhabdomyosarcoma incidence ( J:132943 )

increased mesothelioma incidence ( J:132943 )

homeostasis/metabolism

pleural effusion ( J:132943 )

• following adenoviral cre treatment, the parietal pleura often shows invasion with concomitant pleural effusion

respiratory system

pleural effusion ( J:132943 )

• following adenoviral cre treatment, the parietal pleura often shows invasion with concomitant pleural effusion

muscle

increased rhabdomyosarcoma incidence ( J:132943 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant mesothelioma		DOID:1790	OMIM:156240	J:132943

Genotype
MGI:3850409

cn14

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Trp53^tm1Brd/Trp53⁺; Tg(Mpz-cre)3Brn/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N

mortality/aging

decreased survivor rate ( J:92413 )

premature death ( J:92413 )

• 4 of 12 mice die prematurely due to malignant peripheral nerve sheath tumors, 3 of which are 5 months old

neoplasm

increased neurofibrosarcoma incidence ( J:92413 )

• in 4 of 12 mice

nervous system

increased neurofibrosarcoma incidence ( J:92413 )

• in 4 of 12 mice

Genotype
MGI:3850407

cn15

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Trp53^tm1Brd/Trp53⁺; Tg(Mpz-cre)2Brn/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N

mortality/aging

decreased survivor rate ( J:92413 )

premature death ( J:92413 )

• median age of death is 4.5 months

neoplasm

osseous metaplasia ( J:92413 )

• 23% of mice develop osseous metaplasia

increased sarcoma incidence ( J:92413 )

• one mouse developed lymphosarcoma

increased leiomyosarcoma incidence ( J:92413 )

• in 8% of mice with metastasis to the liver

increased nervous system tumor incidence ( J:92413 )

• 85% of mice develop peripheral nerve tumors

increased neurofibroma incidence ( J:92413 )

• 8% of mice develop neurofibroma

increased neurofibrosarcoma incidence ( J:92413 )

• 77% of mice develop peripheral nerve tumors from peripheral nerves of the limbs and from the dorsal root ganglia

increased Schwannoma incidence ( J:92413 )

• 11% of mice develop schwannoma

skeleton

abnormal tooth development ( J:92413 )

• 35% of mice exhibit odontoblastic hyperplasia

abnormal osteoblast morphology ( J:92413 )

• 15% of mice develop osteogenic hyperplasia

nervous system

abnormal Schwann cell morphology ( J:92413 )

• 81% of mice exhibit Schwann cell hyperplasia with increased incidence of diffuse Schwann cell hyperplasia in major peripheral nerve trunks

increased nervous system tumor incidence ( J:92413 )

• 85% of mice develop peripheral nerve tumors

increased neurofibroma incidence ( J:92413 )

• 8% of mice develop neurofibroma

increased neurofibrosarcoma incidence ( J:92413 )

• 77% of mice develop peripheral nerve tumors from peripheral nerves of the limbs and from the dorsal root ganglia

increased Schwannoma incidence ( J:92413 )

• 11% of mice develop schwannoma

renal/urinary system

abnormal renal tubule morphology ( J:92413 )

• 73% of mice exhibit renal tubular cell hyperplasia

vision/eye

cataract ( J:92413 )

• 85% of mice

craniofacial

abnormal tooth development ( J:92413 )

• 35% of mice exhibit odontoblastic hyperplasia

growth/size/body

abnormal tooth development ( J:92413 )

• 35% of mice exhibit odontoblastic hyperplasia

muscle

increased leiomyosarcoma incidence ( J:92413 )

• in 8% of mice with metastasis to the liver

cellular

abnormal Schwann cell morphology ( J:92413 )

• 81% of mice exhibit Schwann cell hyperplasia with increased incidence of diffuse Schwann cell hyperplasia in major peripheral nerve trunks

Genotype
MGI:3850410

cn16

• Allelic Composition: Nf2^tm2Gth/Nf2⁺; Trp53^tm1Brd/Trp53⁺; Tg(Mpz-cre)3Brn/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N

mortality/aging

premature death ( J:92413 )

• mice exhibit a decrease in survival rate when the Nf2 and Trp53 alleles are carried in cis as opposed to trans, but live longer than conditional mutants carrying Tg(P0-Cre)2Gth

neoplasm

increased neurofibrosarcoma incidence ( J:92413 )

• between 3.5 and 13.5 months,19% of mice develop malignant peripheral nerve sheath tumors when the Nf2 and Trp53 alleles are carried in cis

• however, no tumors form in mice when the Nf2 and Trp53 alleles are carried in trans

increased skeletal tumor incidence ( J:92413 )

• when the Nf2 and Trp53 alleles are carried in trans mice develop osteogenic tumors not restricted to neural crest-derived bone

increased osteosarcoma incidence ( J:92413 )

• 81% of mice develop osteogenic (osteomas and osteosarcomas) tumors when the Nf2 and Trp53 alleles are carried in cis

increased osteoma incidence ( J:92413 )

• 81% of mice develop osteogenic (osteomas and osteosarcomas) tumors when the Nf2 and Trp53 alleles are carried in cis

skeleton

increased skeletal tumor incidence ( J:92413 )

• when the Nf2 and Trp53 alleles are carried in trans mice develop osteogenic tumors not restricted to neural crest-derived bone

increased osteosarcoma incidence ( J:92413 )

• 81% of mice develop osteogenic (osteomas and osteosarcomas) tumors when the Nf2 and Trp53 alleles are carried in cis

increased osteoma incidence ( J:92413 )

• 81% of mice develop osteogenic (osteomas and osteosarcomas) tumors when the Nf2 and Trp53 alleles are carried in cis

nervous system

increased neurofibrosarcoma incidence ( J:92413 )

• between 3.5 and 13.5 months,19% of mice develop malignant peripheral nerve sheath tumors when the Nf2 and Trp53 alleles are carried in cis

• however, no tumors form in mice when the Nf2 and Trp53 alleles are carried in trans

Genotype
MGI:3850408

cn17

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Trp53^tm1Brd/Trp53^tm1Brd; Tg(Mpz-cre)2Brn/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N

mortality/aging

premature death ( J:92413 )

• mice die a few months of birth

neoplasm

osseous metaplasia ( J:92413 )

• 38% of mice develop osseous metaplasia

increased tumor incidence ( J:92413 )

increased sarcoma incidence ( J:92413 )

• at 2 to 3.5 months, 25% of mice develop 4 sarcoma mainly in the ganglia

increased rhabdomyosarcoma incidence ( J:92413 )

• in one mouse

increased neurofibrosarcoma incidence ( J:92413 )

• at 2 to 3.5 months, 50% of mice develop 4 malignant peripheral nerve sheath tumors

increased extremity angiosarcoma incidence ( J:92413 )

• in 63% of mice

increased osteosarcoma incidence ( J:92413 )

• in one mouse

increased osteoma incidence ( J:92413 )

• one mouse developed osteomas

skeleton

increased osteosarcoma incidence ( J:92413 )

• in one mouse

increased osteoma incidence ( J:92413 )

• one mouse developed osteomas

abnormal osteoblast morphology ( J:92413 )

• 25% of mice develop osteogenic hyperplasia

nervous system

abnormal Schwann cell morphology ( J:92413 )

• 38% of mice exhibit Schwann cell hyperplasia

increased neurofibrosarcoma incidence ( J:92413 )

• at 2 to 3.5 months, 50% of mice develop 4 malignant peripheral nerve sheath tumors

renal/urinary system

abnormal renal tubule morphology ( J:92413 )

• 63% of mice exhibit renal tubular cell hyperplasia

vision/eye

cataract ( J:92413 )

• 75% of mice

muscle

increased rhabdomyosarcoma incidence ( J:92413 )

• in one mouse

cellular

abnormal Schwann cell morphology ( J:92413 )

• 38% of mice exhibit Schwann cell hyperplasia

Genotype
MGI:3850479

cn18

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

neoplasm

increased renal carcinoma incidence ( J:150071 )

• within 6 months of induction, lumen-filling renal tubule neoplasias are observed unlike in control mice

• tumors often block urinary flow

renal/urinary system

increased renal carcinoma incidence ( J:150071 )

• within 6 months of induction, lumen-filling renal tubule neoplasias are observed unlike in control mice

• tumors often block urinary flow

Genotype
MGI:4819843

cn19

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Yap1^tm1.1Dupa/Yap1⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:162628 )

N • mice do not exhibit bile duct proliferation

enlarged liver ( J:162628 )

• slightly

neoplasm

neoplasm ( J:162628 )

N • mice do not develop bile duct hamartomas or hepatocellular carcinoma

growth/size/body

enlarged liver ( J:162628 )

• slightly

Genotype
MGI:4819842

cn20

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Yap1^tm1.1Dupa/Yap1^tm1.1Dupa; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:162628 )

N • liver is as enlarge as in Nf2^tm2Gth/Nf2^tm2Gth Tg(Alb-cre)21Mgn mice

N • bile over-proliferation observed in Nf2^tm2Gth/Nf2^tm2Gth Tg(Alb-cre)21Mgn mice is suppressed

neoplasm

neoplasm ( J:162628 )

N • mice do not develop bile duct hamartomas or hepatocellular carcinoma unlike Nf2^tm2Gth/Nf2^tm2Gth Tg(Alb-cre)21Mgn mice

Genotype
MGI:4819845

cn21

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

liver/biliary system

bile duct hyperplasia ( J:162628 )

bile duct proliferation ( J:162628 )

abnormal liver morphology ( J:162628 )

• at E18.5, multiple tubular structures surround each portal vein unlike in wild-type mice

enlarged liver ( J:162628 )

increased hepatobiliary system tumor incidence ( J:162628 )

• mice exhibit widespread bile duct hamartomas that expand into the deep liver parenchyma unlike wild-type mice

increased hepatocellular carcinoma incidence ( J:162628 )

• at 1 year of age

neoplasm

increased hepatobiliary system tumor incidence ( J:162628 )

• mice exhibit widespread bile duct hamartomas that expand into the deep liver parenchyma unlike wild-type mice

increased hepatocellular carcinoma incidence ( J:162628 )

• at 1 year of age

endocrine/exocrine glands

bile duct hyperplasia ( J:162628 )

bile duct proliferation ( J:162628 )

growth/size/body

enlarged liver ( J:162628 )

Genotype
MGI:3850478

cn22

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(Vil1-cre)20Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

mortality/aging

premature death ( J:150071 )

• mice die by 10 months of age

lethality throughout fetal growth and development, incomplete penetrance ( J:150071 )

• mice occasionally die between E17 and P3

perinatal lethality, incomplete penetrance ( J:150071 )

• mice occasionally die between E17 and P3

postnatal lethality, incomplete penetrance ( J:150071 )

• mice occasionally die between E17 and P3

• fewer than expected mice survive until weaning

neoplasm

increased renal carcinoma incidence ( J:150071 )

• lesions in the renal tubule epithelia are observed as early as 15 days of age with most initiating in the corticomedullary junctions as projections of atypical epithelial cells into the proximal convoluted tubule lumen

• by 3 months of age, all mice develop lumen-filling intratubular neoplasia unlike wild-type mice

• by 6 months, tumors increase in size and number penetrating tubule basement membrane as invasive carcinomas

• renal tubule carcinoma cells exhibit a 7-fold increase in proliferation compared to in Nf2^tm2Gth homozygotes

• however, treatment with erlotinib reduces cell proliferation

growth/size/body

decreased body size ( J:150071 )

renal/urinary system

increased renal carcinoma incidence ( J:150071 )

• lesions in the renal tubule epithelia are observed as early as 15 days of age with most initiating in the corticomedullary junctions as projections of atypical epithelial cells into the proximal convoluted tubule lumen

• by 3 months of age, all mice develop lumen-filling intratubular neoplasia unlike wild-type mice

• by 6 months, tumors increase in size and number penetrating tubule basement membrane as invasive carcinomas

• renal tubule carcinoma cells exhibit a 7-fold increase in proliferation compared to in Nf2^tm2Gth homozygotes

• however, treatment with erlotinib reduces cell proliferation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
renal cell carcinoma		DOID:4450	OMIM:300854	J:150071

Genotype
MGI:4819847

cn23

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

vision/eye

abnormal lens morphology ( J:162628 )

• ectopic cells accumulate in the equator and posterior of the lens unlike in wild-type mice

abnormal lens epithelium morphology ( J:162628 )

• in the anterior region

cataract ( J:162628 )

Genotype
MGI:3850391

cn24

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(Mpz-cre)4Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

decreased survivor rate ( J:63264 )

premature death ( J:63264 )

• all mice die by 19 months of age

neoplasm

increased Schwannoma incidence ( J:63264 )

• 66% of mice develop schwannomas

nervous system

increased Schwannoma incidence ( J:63264 )

• 66% of mice develop schwannomas

Genotype
MGI:3850412

cn25

• Allelic Composition: Cdkn2a^tm1.1Brn/Cdkn2a^tm1.1Brn; Nf2^tm2Gth/Nf2^tm2Gth
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

neoplasm

increased liver tumor incidence ( J:131179 )

• following adenoviral cre treatment, liver tumor development is increased compared to in untreated mice (on average 18% from 3%)

osseous metaplasia ( J:131179 )

• following treatment with adenoviral cre, 15% of mice exhibit osseous metaplasia compared to 2% of wild-type mice

increased meningioma incidence ( J:131179 )

• following treatment with adenoviral cre, meningioma development is increased compared to in untreated mice (on average 37% from 13%)

• meningiomas in adenoviral cre-treated mice share radiological features with human meningiomas

increased osteoma incidence ( J:131179 )

• following treatment with adenoviral cre, osteoma development is increased compared to in untreated mice (on average 78% from 57%)

nervous system

increased meningioma incidence ( J:131179 )

• following treatment with adenoviral cre, meningioma development is increased compared to in untreated mice (on average 37% from 13%)

• meningiomas in adenoviral cre-treated mice share radiological features with human meningiomas

hydrocephaly ( J:131179 )

• following adenoviral cre treatment, hydrocephalus is increased compared to in untreated mice (on average 56% from 36%)

abnormal meninges morphology ( J:131179 )

• following adenoviral cre treatment, meningothelial proliferation is increased compared to in untreated mice (on average 77% from 46%)

skeleton

increased osteoma incidence ( J:131179 )

• following treatment with adenoviral cre, osteoma development is increased compared to in untreated mice (on average 78% from 57%)

liver/biliary system

increased liver tumor incidence ( J:131179 )

• following adenoviral cre treatment, liver tumor development is increased compared to in untreated mice (on average 18% from 3%)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial meningioma		DOID:4586		J:131179

Genotype
MGI:3850388

cn26

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(Mpz-cre)1Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

decreased survivor rate ( J:63264 )

premature death ( J:63264 )

• mice have a short lifespan dying by 10 months of age

postnatal lethality, incomplete penetrance ( J:63264 )

• fewer mice than expected are obtained (no time point for lethality given)

• however, postnatal lethality can be partially rescued by supplementing food with porridge

reproductive system

infertility ( J:63264 )

neoplasm

increased tumor incidence ( J:63264 )

• after 10 months, mice develop benign and malignant Schwann cell tumors

craniofacial

delayed tooth eruption ( J:63264 )

• at P17 and P19, molar eruption is retarded or absent

failure of tooth eruption ( J:63264 )

• at P17 and P19, molar eruption is retarded or absent

nervous system

abnormal Schwann cell morphology ( J:63264 )

• 2 of 4 mice and 4 months and 1 mouse at P17 exhibit hyperplasia or hypertrophy in Schwann cells of distal peripheral nerves

• at P19 and P33, Schwann cells are without a clear relation with an axon and many of the myelin sheaths herniated and loop into the central axonal region unlike in wild-type mice

growth/size/body

delayed tooth eruption ( J:63264 )

• at P17 and P19, molar eruption is retarded or absent

failure of tooth eruption ( J:63264 )

• at P17 and P19, molar eruption is retarded or absent

decreased body size ( J:63264 )

decreased body weight ( J:63264 )

hearing/vestibular/ear

increased susceptibility to otitis media ( J:63264 )

immune system

increased susceptibility to otitis media ( J:63264 )

skeleton

delayed tooth eruption ( J:63264 )

• at P17 and P19, molar eruption is retarded or absent

failure of tooth eruption ( J:63264 )

• at P17 and P19, molar eruption is retarded or absent

cellular

abnormal Schwann cell morphology ( J:63264 )

• 2 of 4 mice and 4 months and 1 mouse at P17 exhibit hyperplasia or hypertrophy in Schwann cells of distal peripheral nerves

• at P19 and P33, Schwann cells are without a clear relation with an axon and many of the myelin sheaths herniated and loop into the central axonal region unlike in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
otitis media		DOID:10754		J:63264

Genotype
MGI:3850405

cn27

• Allelic Composition: Nf2^tm2Gth/Nf2⁺; Tg(Mpz-cre)#Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

endocrine/exocrine glands

increased fibroadenoma incidence ( J:63264 )

• 6% of mice exhibit fibroadenoma in the mammary gland

neoplasm

increased fibroadenoma incidence ( J:63264 )

• 6% of mice exhibit fibroadenoma in the mammary gland

increased lung adenocarcinoma incidence ( J:63264 )

• in 31% in mice

increased osteoma incidence ( J:63264 )

• 6% of mice develop osteoma

integument

increased fibroadenoma incidence ( J:63264 )

• 6% of mice exhibit fibroadenoma in the mammary gland

nervous system

nervous system phenotype ( J:63264 )

N • mice exhibit normal Schwann cell proliferation

respiratory system

increased lung adenocarcinoma incidence ( J:63264 )

• in 31% in mice

craniofacial

abnormal tooth development ( J:63264 )

• 6% of mice exhibit odontoblastic hyperplasia

skeleton

abnormal tooth development ( J:63264 )

• 6% of mice exhibit odontoblastic hyperplasia

increased osteoma incidence ( J:63264 )

• 6% of mice develop osteoma

growth/size/body

abnormal tooth development ( J:63264 )

• 6% of mice exhibit odontoblastic hyperplasia

Genotype
MGI:3850403

cn28

• Allelic Composition: Nf2^tm1Gth/Nf2^tm2Gth; Tg(Mpz-cre)#Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

decreased survivor rate ( J:63264 )

• mice exhibit reduced viability

neoplasm

osseous metaplasia ( J:63264 )

• mice exhibit osseous metaplasia in the lung, brain, kidney, and nasal mucosa

increased neurofibrosarcoma incidence ( J:63264 )

increased mesothelioma incidence ( J:63264 )

• one mouse developed a mesothelioma

increased odontoma incidence ( J:63264 )

• 9% of mice develop odontomas and odontosarcomas

increased odontosarcoma incidence ( J:63264 )

• 9% of mice develop odontomas and odontosarcomas

increased Schwannoma incidence ( J:63264 )

• mice develop Schwann cell tumors

skeleton

abnormal tooth development ( J:63264 )

• mice exhibit odontoblastic hyperplasia

abnormal osteoblast morphology ( J:63264 )

• osteoblastic hyperplasia

nervous system

abnormal Schwann cell morphology ( J:63264 )

• 59% of mice exhibit Schwann cell hyperplasia

increased neurofibrosarcoma incidence ( J:63264 )

increased Schwannoma incidence ( J:63264 )

• mice develop Schwann cell tumors

renal/urinary system

abnormal renal tubule morphology ( J:63264 )

• mice exhibit renal tubular cell hyperplasia

craniofacial

abnormal tooth development ( J:63264 )

• mice exhibit odontoblastic hyperplasia

growth/size/body

abnormal tooth development ( J:63264 )

• mice exhibit odontoblastic hyperplasia

cellular

abnormal Schwann cell morphology ( J:63264 )

• 59% of mice exhibit Schwann cell hyperplasia

Genotype
MGI:3850390

cn29

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(Mpz-cre)3Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

neoplasm

increased fibroadenoma incidence ( J:63264 )

• 12% of mice exhibit fibroadenoma in the mammary gland

osseous metaplasia ( J:63264 )

• 30% of mice develop osseous metaplasia

increased lung adenocarcinoma incidence ( J:63264 )

• in 12% in mice

increased renal carcinoma incidence ( J:63264 )

• 18% of mice develop carcinoma in situ in the kidney

increased sarcoma incidence ( J:63264 )

• 30% of mice develop stromal sarcoma

increased neurofibrosarcoma incidence ( J:63264 )

• 6% of mice develop neurofibrosarcoma

increased osteosarcoma incidence ( J:63264 )

• in 6% of mice

increased odontoma incidence ( J:63264 )

• 6% of mice exhibit odontoma

increased Schwannoma incidence ( J:63264 , J:92413 )

• 30% of mice develop osseous metaplasia (J:63264)

• 6% of mice exhibit odontoma (J:63264)

• 35% of mice develop schwannomas (J:92413)

increased osteoma incidence ( J:63264 )

• 6% of mice develop osteoma

skeleton

abnormal tooth development ( J:63264 )

• 12% of mice exhibit odontoblastic hyperplasia

increased osteosarcoma incidence ( J:63264 )

• in 6% of mice

increased osteoma incidence ( J:63264 )

• 6% of mice develop osteoma

abnormal osteoblast morphology ( J:63264 )

• osteogenic hyperplasia in 47% of mice

nervous system

abnormal Schwann cell morphology ( J:63264 )

• 82% of mice exhibit Schwann cell hyperplasia

increased neurofibrosarcoma incidence ( J:63264 )

• 6% of mice develop neurofibrosarcoma

increased Schwannoma incidence ( J:63264 , J:92413 )

• 30% of mice develop osseous metaplasia (J:63264)

• 6% of mice exhibit odontoma (J:63264)

• 35% of mice develop schwannomas (J:92413)

renal/urinary system

increased renal carcinoma incidence ( J:63264 )

• 18% of mice develop carcinoma in situ in the kidney

abnormal renal tubule morphology ( J:63264 )

• 53% of mice exhibit renal tubular cell hyperplasia

vision/eye

cataract ( J:63264 )

• in 14% to 18% of mice, in which 50% of cases are bilateral

craniofacial

abnormal tooth development ( J:63264 )

• 12% of mice exhibit odontoblastic hyperplasia

growth/size/body

abnormal tooth development ( J:63264 )

• 12% of mice exhibit odontoblastic hyperplasia

respiratory system

increased lung adenocarcinoma incidence ( J:63264 )

• in 12% in mice

integument

increased fibroadenoma incidence ( J:63264 )

• 12% of mice exhibit fibroadenoma in the mammary gland

endocrine/exocrine glands

increased fibroadenoma incidence ( J:63264 )

• 12% of mice exhibit fibroadenoma in the mammary gland

cellular

abnormal Schwann cell morphology ( J:63264 )

• 82% of mice exhibit Schwann cell hyperplasia

Genotype
MGI:3850389

cn30

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(Mpz-cre)2Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

decreased survivor rate ( J:63264 )

premature death ( J:63264 )

• few mice survive beyond 24 months of age

postnatal lethality, incomplete penetrance ( J:63264 )

• fewer mice than expected are obtained (no time point for lethality given)

growth/size/body

abnormal tooth development ( J:92413 )

• one mouse exhibited odontoblastic hyperplasia

decreased body size ( J:63264 )

• although not as much as in Tg(P0-Cre)1Gth conditional knock-outs of Nf2

decreased body weight ( J:63264 )

• although not as much as in Tg(P0-Cre)1Gth conditional knock-outs of Nf2

nervous system

abnormal Schwann cell morphology ( J:63264 , J:92413 )

• mice exhibit Schwann cell hyperplasia (J:63264)

• occasionally whorls of thin cytoplasmic processes are observed in Schwann cells (J:63264)

• 100% of mice exhibit Schwann cell hyperplasia (J:92413)

increased neurofibrosarcoma incidence ( J:92413 )

• 1 of 27 mice develop peripheral nerve tumors

increased Schwannoma incidence ( J:63264 , J:92413 )

• 4% of mice develop schwannomas (J:63264)

neoplasm

osseous metaplasia ( J:92413 )

• 25% of mice develop osseous metaplasia

increased lung adenocarcinoma incidence ( J:92413 )

• in one mouse

increased renal carcinoma incidence ( J:92413 )

• 25% of mice develop carcinoma in situ in the kidney

increased neurofibrosarcoma incidence ( J:92413 )

• 1 of 27 mice develop peripheral nerve tumors

increased extremity angiosarcoma incidence ( J:92413 )

• in one mouse

increased Schwannoma incidence ( J:63264 , J:92413 )

• 4% of mice develop schwannomas (J:63264)

skeleton

abnormal tooth development ( J:92413 )

• one mouse exhibited odontoblastic hyperplasia

abnormal osteoblast morphology ( J:92413 )

• 25% of mice develop osteogenic hyperplasia

renal/urinary system

increased renal carcinoma incidence ( J:92413 )

• 25% of mice develop carcinoma in situ in the kidney

abnormal renal tubule morphology ( J:92413 )

• 25% of mice develop carcinoma in situ in the kidney

vision/eye

cataract ( J:63264 , J:92413 )

• in 59% of mice, in which 50% of cases are bilateral (J:63264)

• 86% of mice (J:92413)

hearing/vestibular/ear

increased susceptibility to otitis media ( J:63264 )

immune system

increased susceptibility to otitis media ( J:63264 )

craniofacial

abnormal tooth development ( J:92413 )

• one mouse exhibited odontoblastic hyperplasia

respiratory system

increased lung adenocarcinoma incidence ( J:92413 )

• in one mouse

cellular

abnormal Schwann cell morphology ( J:63264 , J:92413 )

• mice exhibit Schwann cell hyperplasia (J:63264)

• occasionally whorls of thin cytoplasmic processes are observed in Schwann cells (J:63264)

• 100% of mice exhibit Schwann cell hyperplasia (J:92413)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
otitis media		DOID:10754		J:63264

Genotype
MGI:3850402

cn31

• Allelic Composition: Nf2^tm1Gth/Nf2^tm2Gth; Tg(Mpz-cre)4Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

decreased survivor rate ( J:63264 )

Genotype
MGI:5051641

cn32

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Ptgds^{tm1.1(cre)Gvn}/Ptgds⁺
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

endocrine/exocrine glands

increased pituitary adenoma incidence ( J:173718 )

• observed in 69% of mice examined

mortality/aging

mortality/aging ( J:173718 )

N • mice are born at normal Mendelian frequencies, are viable, and show comparable survival to control littermates (>75% survive to 10 months)

neoplasm

increased pituitary adenoma incidence ( J:173718 )

• observed in 69% of mice examined

increased meningioma incidence ( J:173718 )

• meningiomas are frequently observed; development is restricted to base of skull ventral to brainstem

increased osteoma incidence ( J:173718 )

• observed in 81% of mice examined

nervous system

increased pituitary adenoma incidence ( J:173718 )

• observed in 69% of mice examined

increased meningioma incidence ( J:173718 )

• meningiomas are frequently observed; development is restricted to base of skull ventral to brainstem

skeleton

increased osteoma incidence ( J:173718 )

• observed in 81% of mice examined

Genotype
MGI:5051643

cn33

• Allelic Composition: Cdkn2a^tm1.1Brn/Cdkn2a^tm1.1Brn; Nf2^tm2Gth/Nf2^tm2Gth; Ptgds^{tm1.1(cre)Gvn}/Ptgds⁺
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

nervous system

increased meningioma incidence ( J:173718 )

• mice develop a slightly higher number of meningiomas (not statistically significant) relative to Cdkn2a-sufficient animals

mortality/aging

mortality/aging ( J:173718 )

N • mice show similar survival/lifespan to Cdkn2a-sufficient animals

neoplasm

neoplasm ( J:173718 )

N • no pituitary tumors are observed

increased meningioma incidence ( J:173718 )

• mice develop a slightly higher number of meningiomas (not statistically significant) relative to Cdkn2a-sufficient animals

Genotype
MGI:5051644

cn34

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Ptgds^{tm1.1(cre)Gvn}/Ptgds⁺; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

premature death ( J:173718 )

• survival is significantly shortened relative to Trp53-sufficient Nf2-deficient mice (almost complete mortality by about 7 months of age)

neoplasm

increased osteosarcoma incidence ( J:173718 )

• mice develop aggressive osteosarcomas early in life, likely reducing survival time

increased nervous system tumor incidence ( J:173718 )

• development of malignant peripheral nerve sheath tumours (MPNST) and choroid plexus carcinoma is also seen in some animals, likely reducing survival time

skeleton

increased osteosarcoma incidence ( J:173718 )

• mice develop aggressive osteosarcomas early in life, likely reducing survival time

nervous system

increased nervous system tumor incidence ( J:173718 )

• development of malignant peripheral nerve sheath tumours (MPNST) and choroid plexus carcinoma is also seen in some animals, likely reducing survival time

Genotype
MGI:3850395

cn35

• Allelic Composition: Nf2^tm1Gth/Nf2^tm2Gth; Tg(Mpz-cre)3Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

decreased survivor rate ( J:63264 )

Genotype
MGI:3850394

cn36

• Allelic Composition: Nf2^tm1Gth/Nf2^tm2Gth; Tg(Mpz-cre)2Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

decreased survivor rate ( J:63264 )

premature death ( J:63264 )

• 50% of mice die within the first year

craniofacial

delayed tooth eruption ( J:63264 )

• retarded or absent

failure of tooth eruption ( J:63264 )

• retarded or absent

growth/size/body

delayed tooth eruption ( J:63264 )

• retarded or absent

failure of tooth eruption ( J:63264 )

• retarded or absent

decreased body size ( J:63264 )

decreased body weight ( J:63264 )

hearing/vestibular/ear

increased susceptibility to otitis media ( J:63264 )

immune system

increased susceptibility to otitis media ( J:63264 )

skeleton

delayed tooth eruption ( J:63264 )

• retarded or absent

failure of tooth eruption ( J:63264 )

• retarded or absent

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
otitis media		DOID:10754		J:63264

Genotype
MGI:3850393

cn37

• Allelic Composition: Nf2^tm1Gth/Nf2^tm2Gth; Tg(Mpz-cre)1Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:63264 )

• the few mice that are produced die prior to weaning

nervous system

abnormal Schwann cell morphology ( J:63264 )

• at P17, one mouse exhibited a subcutaneous Schwann cell nodule

neoplasm

increased hamartoma incidence ( J:63264 )

• at P19, one mouse exhibited a hamartoma of the olfactory bulb composed of Schwann and neural cells

cellular

abnormal Schwann cell morphology ( J:63264 )

• at P17, one mouse exhibited a subcutaneous Schwann cell nodule

Genotype
MGI:3850392

cn38

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(Mpz-cre)#Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

neoplasm

osseous metaplasia ( J:63264 )

• mice exhibit osseous metaplasia in the lung, brain, kidney, and nasal mucosa

increased renal carcinoma incidence ( J:63264 )

• 10% of mice develop carcinoma in situ in the kidney

increased neurofibrosarcoma incidence ( J:63264 )

increased osteosarcoma incidence ( J:63264 )

• 8% of mice develop osteomas and osteosarcomas

increased odontoma incidence ( J:63264 )

• 6% of mice develop odontomas and odontosarcomas

increased odontosarcoma incidence ( J:63264 )

• 6% of mice develop odontomas and odontosarcomas

increased osteoma incidence ( J:63264 )

• 8% of mice develop osteomas and osteosarcomas

skeleton

abnormal tooth development ( J:63264 )

• mice exhibit odontoblastic hyperplasia

increased osteosarcoma incidence ( J:63264 )

• 8% of mice develop osteomas and osteosarcomas

increased osteoma incidence ( J:63264 )

• 8% of mice develop osteomas and osteosarcomas

abnormal osteoblast morphology ( J:63264 )

• osteoblastic hyperplasia

nervous system

abnormal Schwann cell morphology ( J:63264 )

• 8% of mice exhibit Schwann cell hyperplasia

increased neurofibrosarcoma incidence ( J:63264 )

renal/urinary system

increased renal carcinoma incidence ( J:63264 )

• 10% of mice develop carcinoma in situ in the kidney

abnormal renal tubule morphology ( J:63264 )

• mice exhibit renal tubular cell hyperplasia

craniofacial

abnormal tooth development ( J:63264 )

• mice exhibit odontoblastic hyperplasia

growth/size/body

abnormal tooth development ( J:63264 )

• mice exhibit odontoblastic hyperplasia

cellular

abnormal Schwann cell morphology ( J:63264 )

• 8% of mice exhibit Schwann cell hyperplasia

Genotype
MGI:5784767

cn39

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/NCr

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:231492 )

• about 65% of mice exhibit mild nodular hyperplasia after 18 months

neoplasm

neoplasm ( J:231492 )

N • mice do not develop thyroid cancer

Genotype
MGI:5619302

cn40

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(Postn-cre)1Sjc/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/NTac

mortality/aging

premature death ( J:216420 )

• mice show reduced life span

behavior/neurological

impaired righting response ( J:216420 )

• mice exhibit difficulty in righting themselves

impaired swimming ( J:216420 )

trunk curl ( J:216420 )

• in the trunk curl test, mice do not reach for the horizontal platform when suspended by the tail and tend to curl in toward their abdomen

head bobbing ( J:216420 )

head tilt ( J:216420 )

head tossing ( J:216420 )

circling ( J:216420 )

hearing/vestibular/ear

decreased auditory brainstem response wave amplitude ( J:216420 )

• ABR waveform analysis indicates a reduction in the first ABR wave amplitude at 6 and 8 months of age and a reduction in summating potential amplitude at 10 months of age, indicating a functional disruption in the cochlear synapse and/or cochlear nerve

increased or absent threshold for auditory brainstem response ( J:216420 )

• mice exhibit a progressive increase in ABR threshold

sensorineural hearing loss ( J:216420 )

• sensorineural hearing loss that is temporally correlated with tumorigenesis

nervous system

increased Schwann cell number ( J:216420 )

• Schwann cell hyperplasia in the spinal ganglion

increased neurofibrosarcoma incidence ( J:216420 )

• most mice show only multiple large schwannomas, but 5 of 16 mice show tumor lesions consistent with malignant peripheral nerve sheath tumors

increased Schwannoma incidence ( J:216420 )

• mice develop slow-growing, low-grade schwannomas that are seen by 5 months of age

• schwannomas are seen in the dorsal root ganglion and proximal spine nerve by 8 months, and in peripheral, cranial, and spinal nerves (such as of the trigeminal and facial nerves) by 10 months

• aberrant Schwann cell growth is seen in cranial nerve VIII proximal to its entry into the inner ear, including tumors in Scarpas ganglion

• all mice exhibit vestibular schwannomas

enlarged dorsal root ganglion ( J:216420 )

• by 5 months of age, all mice show enlargement of the dorsal root ganglion

abnormal spinal nerve morphology ( J:216420 )

• by 5 months of age, all mice show enlargement of the proximal spinal nerve roots

neoplasm

increased neurofibrosarcoma incidence ( J:216420 )

• most mice show only multiple large schwannomas, but 5 of 16 mice show tumor lesions consistent with malignant peripheral nerve sheath tumors

increased Schwannoma incidence ( J:216420 )

• mice develop slow-growing, low-grade schwannomas that are seen by 5 months of age

• schwannomas are seen in the dorsal root ganglion and proximal spine nerve by 8 months, and in peripheral, cranial, and spinal nerves (such as of the trigeminal and facial nerves) by 10 months

• aberrant Schwann cell growth is seen in cranial nerve VIII proximal to its entry into the inner ear, including tumors in Scarpas ganglion

• all mice exhibit vestibular schwannomas

cellular

increased Schwann cell number ( J:216420 )

• Schwann cell hyperplasia in the spinal ganglion

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
vestibular schwannomatosis		DOID:0111252	OMIM:101000	J:216420