All Phenotypes Cdkn2a<tm1Rdp> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Cdkn2a^tm1Rdp
targeted mutation 1, Ronald DePinho
MGI:1857942

Summary

49 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp	FVB.Cg-Cdkn2a^tm1Rdp	MGI:3714117
hm2	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp	involves: 129/Sv * C57BL/6 * C57BL/6J * SJL	MGI:4420542
hm3	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp	involves: 129/Sv * C57BL/6J * FVB/N * SJL	MGI:3033701
hm4	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp	involves: 129/Sv * C57BL/6J * SJL	MGI:4830507
hm5	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp	involves: 129/Sv * C57BL/6 * SJL	MGI:2175771
cn6	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Rnf2^tm1Mvi/Rnf2^tm1Mvi Tg(Mx1-cre)1Cgn/0	involves: 129 * C57BL/6 * C57BL/10 * CBA * SJL	MGI:3772194
cn7	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor⁺ Pdgfra^tm12Sor/Pdgfra⁺	involves: 129 * C57BL/6J * SJL	MGI:3838621
cn8	Braf^tm1Cpri/Braf^tm1Cpri Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-cre/ERT2)1Lru/0	involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * DBA/2 * SJL	MGI:3843342
cn9	Cdkn2a^tm1Rdp/Cdkn2a⁺ Tg(CAG-Bgeo,-tTA,-EGFP)2A11Kuw/0 Tg(Pdx1-cre)6Tuv/0 Tg(tetO-MYC)36Bop/0	involves: 129/Sv * 129P2/OlaHsd * C57BL/6J * FVB/N * SJL	MGI:5521487
cn10	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Pten^tm1Rps/Pten^tm1Rps Tg(Tyr-cre/ERT2)13Bos/0	involves: 129/Sv * 129S1/Sv * C57BL/6J * FVB/N * SJL	MGI:4418448
cn11	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Kras^tm4Tyj/Kras⁺	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB/N * SJL	MGI:5659895
cn12	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Col1a1^{tm1(CAG-EGFR)Char}/Col1a1^{tm2(CAG-EGFR*)Char} Pten^tm1Hwu/Pten^tm1Hwu	involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL	MGI:3837857
cn13	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Col1a1^{tm1(CAG-EGFR)Char}/Col1a1^{tm1(CAG-EGFR)Char} Pten^tm1Hwu/Pten^tm1Hwu	involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL	MGI:3837855
cn14	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Col1a1^{tm2(CAG-EGFR)Char}/Col1a1^{tm2(CAG-EGFR)Char} Pten^tm1Hwu/Pten^tm1Hwu	involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL	MGI:3837856
cn15	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp E4f1^tm1Pisc/E4f1^tm1.1Llca Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a⁺	involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL	MGI:4867863
cn16	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Dicer1^tm1Snj/Dicer1^tm1Snj	involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3809301
cn17	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp X/Tg(Tyr-HRAS)60Lc	involves: 129/Sv * C57BL/6J * CBA/J * SJL	MGI:4835048
cn18	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Ctnnb1^tm1Mmt/Ctnnb1^tm1Mmt Pten^tm1Rps/Pten^tm1Rps Tg(Tyr-cre/ERT2)13Bos/0	involves: 129/Sv * C57BL/6J * FVB * SJL	MGI:4418449
cn19	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor⁺ Pten^tm1Rdp/Pten^tm1Rdp Tg(tetO-BRAF*V600E)29Lc/0 Tg(Tyr-cre/ERT2)13Bos/0	involves: 129/Sv * C57BL/6J * FVB * SJL	MGI:5700641
cx20	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Fbxw11^tm1Nakay/Fbxw11^tm1Nakay	B6.Cg-Cdkn2a^tm1Rdp Fbxw11^tm1Nakay	MGI:6781883
cx21	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(tetO-Nras*Q61K)#Lc/0 Tg(Tyr-rtTA)37Lc/0	FVB.Cg-Cdkn2a^tm1Rdp Tg(tetO-Nras*Q61K)#Lc Tg(Tyr-rtTA)37Lc	MGI:5818051
cx22	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(GFAP-TVA)10Ech/0	involves: 129 * BALB/c * C57BL/6 * FVB/N * SJL	MGI:3835350
cx23	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(NES-TVA)J12Ech/0	involves: 129 * C57BL/6 * FVB/N * SJL	MGI:3835346
cx24	Cdkn2a^tm1Rdp/Cdkn2a⁺ Tg(NES-TVA)J12Ech/0	involves: 129 * C57BL/6 * FVB/N * SJL	MGI:3835347
cx25	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-Kras2)12Hev/0	involves: 129 * C57BL/6J * FVB/N * SJL	MGI:5912294
cx26	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Rnf2^tm1Mvl/Rnf2^tm1Mvl	involves: 129P2/Ola * 129/Sv * C57BL/6J * FVB/N * SJL	MGI:3852547
cx27	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Sox10^tm1Weg/Sox10⁺ Tg(Tyr-NRAS*Q61K)1Bee/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * SJL	MGI:5515809
cx28	Cdkn2a^tm1Rdp/Cdkn2a⁺ Nf1^tm1Tyj/Nf1⁺	involves: 129S2/SvPas * 129S6/SvEvTac	MGI:3776070
cx29	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Nf1^tm1Tyj/Nf1⁺	involves: 129S2/SvPas * 129S6/SvEvTac	MGI:3776069
cx30	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp	involves: 129/Sv * 129S2/SvPas * C57BL/6 * C57BL/6J * SJL	MGI:4420540
cx31	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Lig4^tm1Fwa/Lig4^tm1Fwa	involves: 129/Sv * 129S6/SvEvTac * C57BL/6J * SJL	MGI:3656001
cx32	Cdkn2a^tm1Rdp/Cdkn2a⁺ Lig4^tm1Fwa/Lig4^tm1Fwa	involves: 129/Sv * 129S6/SvEvTac * C57BL/6J * SJL	MGI:3656002
cx33	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Dicer1^tm1Snj/Dicer1^tm1Snj	involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3809300
cx34	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(GFAP-TVA)5Hev/0	involves: 129/Sv * BALB/c * C57BL/6 * FVB/N * SJL	MGI:3835356
cx35	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-NRAS*Q61K)1Bee/?	involves: 129/Sv * C57BL/6 * DBA/2 * SJL	MGI:3768649
cx36	Cdkn2a^tm1Rdp/Cdkn2a⁺ Tg(Tyr-NRAS*Q61K)1Bee/?	involves: 129/Sv * C57BL/6 * DBA/2 * SJL	MGI:3768653
cx37	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(NES-TVA)J12Ech/0	involves: 129/Sv * C57BL/6 * FVB/N * SJL	MGI:3835361
cx38	Cdkn2a^tm1Rdp/Cdkn2a⁺ X/Tg(Tyr-HRAS)60Lc	involves: 129/Sv * C57BL/6J * CBA/J * FVB/N * SJL	MGI:3815142
cx39	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-BRAF*V600E)470Fgh/0	involves: 129/Sv * C57BL/6J * CBA * SJL	MGI:4354207
cx40	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-BRAF*V600E)476Fgh/0	involves: 129/Sv * C57BL/6J * CBA * SJL	MGI:4354208
cx41	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(S100b-v-erbB)4496Waw/0	involves: 129/Sv * C57BL/6J * DBA/2J * FVB/N * SJL	MGI:3822320
cx42	Cdkn2a^tm1Rdp/Cdkn2a⁺ Tg(S100b-v-erbB)4496Waw/0	involves: 129/Sv * C57BL/6J * DBA/2J * FVB/N * SJL	MGI:3822321
cx43	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-NRAS*Q61K)1Bee/0	involves: 129/Sv * C57BL/6J * DBA/2 * SJL	MGI:5515807
cx44	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Mt1-Hgf)19Lmb/0	involves: 129/Sv * C57BL/6J * FVB/N * SJL	MGI:2653473
cx45	Cdkn2a^tm1Rdp/Cdkn2a⁺ Terc^tm1Rdp/Terc^tm1Rdp	involves: 129/Sv * C57BL/6J * SJL	MGI:3719054
cx46	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(tetO-BRAF*V600E)29Lc/0 Tg(Tyr-rtTA)37Lc/0	involves: 129/Sv * C57BL/6J * SJL	MGI:3834745
cx47	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Mxi1^tm1Rdp/Mxi1^tm1Rdp	involves: 129/Sv * C57BL/6J * SJL	MGI:3040778
cx48	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Terc^tm1Rdp/Terc^tm1Rdp	involves: 129/Sv * C57BL/6J * SJL	MGI:3719052
cx49	Cav1^tm1Mls/Cav1^tm1Mls Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp	involves: 129/Sv * C57BL/6 * SJL	MGI:4418482

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp
Genetic Background	FVB.Cg-Cdkn2a^tm1Rdp

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)

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

vision/eye

abnormal lens development ( J:110215 )

• lens fuses with retinal layers

cataract ( J:110215 )

• 94% of mice with either unilateral or bilateral cataracts

microphthalmia ( J:110215 )

• small eyes and abnormal in shape

• first observed embryonically

abnormal posterior eye segment morphology ( J:110215 )

persistent hyperplastic primary vitreous ( J:110215 )

• retrolental cell mass persists after 2 weeks of age

• hyaloid-artery like structures as late as 12 months of age

• primary vitreous membrane fails to regress and continues to develop

• primary vitreous membrane fuses to posterior capsule of the lens

abnormal retina neuronal layer morphology ( J:110215 )

• retinal folds

• progressive attachment of the retrolental mass to the neuroretina

abnormal retina photoreceptor morphology ( J:110215 )

• rosette-like arrangements of dysplastic photoreceptor cells

retina fold ( J:110215 )

• retinal folds are observed as early as E15.5

nervous system

abnormal retina photoreceptor morphology ( J:110215 )

• rosette-like arrangements of dysplastic photoreceptor cells

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp
Genetic Background	involves: 129/Sv * C57BL/6 * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)

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

cellular

abnormal cell physiology ( J:72780 )

• vHaras-induced foci formation in primary keratinocytes is increased compared with similarly treated wild-type cells indicating increased tumorgenicity

delayed cellular replicative senescence ( J:72780 )

• age-related senescence in the epidermis in vivo is moderately decreased compared to in wild-type mice

neoplasm

increased squamous cell carcinoma incidence ( J:72780 )

• 3 of 6 nude mice transplanted with keratinocytes infected with a vHaras-expressing retrovirus develop well differentiated SCCs unlike nude mice receiving similarly treated wild-type cells

integument

abnormal skin physiology ( J:72780 )

• age-related senescence in the epidermis in vivo is moderately decreased compared to in wild-type mice

abnormal keratinocyte physiology ( J:72780 )

• vHaras-induced foci formation in primary keratinocytes is increased compared with similarly treated wild-type cells indicating increased tumorgenicity

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp
Genetic Background	involves: 129/Sv * C57BL/6J * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)

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

mortality/aging

decreased tumor-free survival time ( J:88365 )

• few survive over a year of age due to spontaneous tumors

neoplasm

increased tumor incidence ( J:88365 )

increased lymphoma incidence ( J:88365 )

• 90% of spontaneous tumors that develop in mutants are histiocytic lymphomas involving the spleen, peripancreatic and other lymph nodes or other sites

increased sarcoma incidence ( J:88365 )

• 9% of tumors that develop in mutants are malignant spindle cell neoplasms, most likely soft-tissue sarcomas

cellular

abnormal cell physiology ( J:88365 )

• MEFs are susceptible to oncogenic transformation, show enhanced subcloning efficiency at low density, and resist both RAS- and culture-induced growth arrest

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp
Genetic Background	involves: 129/Sv * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)

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

neoplasm

increased brain tumor incidence ( J:163931 )

• 50% of mice implanted with neural stem cells expressing Ephb2-RFP develop brain tumors indistinguishable form human ependymomas

nervous system

increased brain tumor incidence ( J:163931 )

• 50% of mice implanted with neural stem cells expressing Ephb2-RFP develop brain tumors indistinguishable form human ependymomas

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp
Genetic Background	involves: 129/Sv * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)

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

immune system

abnormal spleen morphology ( J:53805 )

abnormal spleen red pulp morphology ( J:53805 )

• contains numerous megakaryocytes and lymphoblasts

increased spleen white pulp amount ( J:53805 )

• proliferative expansion of white pulp at 2 months of age

hematopoietic system

extramedullary hematopoiesis ( J:53805 )

• abnormal extramedullary hematopoiesis becoming more severe with age

• occurs in nonlymphoid tissue such as the liver in addition to lymphoid tissue

abnormal spleen morphology ( J:53805 )

abnormal spleen red pulp morphology ( J:53805 )

• contains numerous megakaryocytes and lymphoblasts

increased spleen white pulp amount ( J:53805 )

• proliferative expansion of white pulp at 2 months of age

cellular

abnormal cell cycle ( J:53805 )

• size of "S" phase population of MEFs in culture is increased

increased fibroblast proliferation ( J:53805 )

• MEFs in culture grow more rapidly and achieve higher densities

neoplasm

increased tumor incidence ( J:53805 )

• 69% of mice develop spontaneous tumors by 29 weeks of age whereas controls are free of tumors at 36 weeks

• average latency for tumor formation in 2 stage cancer induction is 9 weeks

increased cutaneous melanoma incidence ( J:98545 )

• 4 of 14 mice develop cutaneous melanomas within 12 months of birth

increased B cell derived lymphoma incidence ( J:53805 )

increased sarcoma incidence ( J:53805 )

increased fibrosarcoma incidence ( J:53805 )

increased hemangiosarcoma incidence ( J:53805 )

• angiosarcomas

integument

increased cutaneous melanoma incidence ( J:98545 )

• 4 of 14 mice develop cutaneous melanomas within 12 months of birth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	dysplastic nevus syndrome	DOID:10041		J:53805

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Rnf2^tm1Mvi/Rnf2^tm1Mvi Tg(Mx1-cre)1Cgn/0
Genetic Background	involves: 129 * C57BL/6 * C57BL/10 * CBA * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Rnf2^tm1Mvi mutation (1 available); any Rnf2 mutation (34 available)
Tg(Mx1-cre)1Cgn mutation (10 available)

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

mortality/aging

premature death ( J:130397 )

• mice die at 11 weeks after treatment with pIpC with splenomegalia and hepatomegalia

hematopoietic system

hematopoietic system phenotype ( J:130397 )

N	• the deficits in splenocytes, bone marrow cells and pre-B cells observed in Rnf2^tm1Mvi/Rnf2^tm1Mvi Tg(Mx1-cre)1Cgn mice treated with pIpC at 6 to 12 weeks is not observed

enlarged spleen ( J:130397 )

abnormal common myeloid progenitor cell morphology ( J:130397 )

• following treatment with pIpC at 6 to 12 weeks, mice exhibit an increase in myeloid colony forming units relative to wild-type mice

neoplasm

increased lymphoma incidence ( J:130397 )

• following treatment with pIpC, mice develop lymphomas at an earlier age of onset compared to in Cdkn2a^tm1Rdp homozygotes

liver/biliary system

enlarged liver ( J:130397 )

immune system

enlarged spleen ( J:130397 )

growth/size/body

enlarged liver ( J:130397 )

enlarged spleen ( J:130397 )

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor⁺ Pdgfra^tm12Sor/Pdgfra⁺
Genetic Background	involves: 129 * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Gt(ROSA)26Sor^{tm1(cre/ERT)Nat} mutation (3 available); any Gt(ROSA)26Sor mutation (1034 available)
Pdgfra^tm12Sor mutation (1 available); any Pdgfra mutation (87 available)

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

neoplasm

increased sarcoma incidence ( J:146617 )

• all tamoxifen-treated mice develop sarcomas of the skin or muscle connective tissue after 10 to 19 weeks

increased fibrosarcoma incidence ( J:146617 )

• 2 tamoxifen-treated mice develop large intestinal tumors resembling undifferentiated fibrosarcomas

muscle

skeletal muscle interstitial fibrosis ( J:146617 )

• tamoxifen-treated mice develop muscle fibrosis at 10 to 19 weeks of age

integument

skin fibrosis ( J:146617 )

• tamoxifen-treated mice develop skin fibrosis at 10 to 19 weeks of age

digestive/alimentary system

intestinal fibrosis ( J:146617 )

• after 15 weeks, tamoxifen-treated mice exhibit intestinal fibrosis

Allelic Composition	Braf^tm1Cpri/Braf^tm1Cpri Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-cre/ERT2)1Lru/0
Genetic Background	involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * DBA/2 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Braf^tm1Cpri mutation (0 available); any Braf mutation (62 available)
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(Tyr-cre/ERT2)1Lru mutation (1 available)

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

neoplasm

increased incidence of tumors by chemical induction ( J:147434 )

• tamoxifen-treated mice develop multiple tumors unlike Braf^tm1Cpri/Braf^tm1Cpri Tg(Tyr-cre/ERT2)1Laru mice that develop single tumors

increased skin nevi incidence ( J:147434 )

• tamoxifen-treated mice develop nevi unlike control mice (either treated with only ethanol or lacking one of the alleles)

increased melanoma incidence ( J:147434 )

• 80% of tamoxifen-treated mice develop melanomas within 12 months

• median latency to develop melanomas in a tamoxifen-treated mouse is 7 months

integument

increased skin nevi incidence ( J:147434 )

• tamoxifen-treated mice develop nevi unlike control mice (either treated with only ethanol or lacking one of the alleles)

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:147434 )

• tamoxifen-treated mice develop multiple tumors unlike Braf^tm1Cpri/Braf^tm1Cpri Tg(Tyr-cre/ERT2)1Laru mice that develop single tumors

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a⁺ Tg(CAG-Bgeo,-tTA,-EGFP)2A11Kuw/0 Tg(Pdx1-cre)6Tuv/0 Tg(tetO-MYC)36Bop/0
Genetic Background	involves: 129/Sv * 129P2/OlaHsd * C57BL/6J * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(CAG-Bgeo,-tTA,-EGFP)2A11Kuw mutation (1 available)
Tg(Pdx1-cre)6Tuv mutation (3 available)
Tg(tetO-MYC)36Bop mutation (1 available)

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

neoplasm

increased pancreas tumor incidence ( J:197052 )

• mutants develop pancreatic tumors with a similar tumor latency as in mutants with wild-type Cdkn2a, however mice show an increase in the occurrence of more aggressive primary pancreatic ductal adenocarcinomas (PDACs) that quickly metastasized to the liver

increased pancreatic ductal adenocarcinoma incidence ( J:197052 )

• mutants show an increase in the occurrence of more aggressive primary pancreatic ductal adenocarcinomas

• 77% of mice show invasive PDAC and 85% show poorly differentiated adenocarcinoma

increased metastatic potential ( J:197052 )

• primary pancreatic ductal adenocarcinomas quickly metastasize to the liver

• 67% incidence of metastases to the liver, 18% incidence to the lung, and 15% incidence to the thymus

endocrine/exocrine glands

increased pancreas tumor incidence ( J:197052 )

increased pancreatic ductal adenocarcinoma incidence ( J:197052 )

• mutants show an increase in the occurrence of more aggressive primary pancreatic ductal adenocarcinomas

• 77% of mice show invasive PDAC and 85% show poorly differentiated adenocarcinoma

mortality/aging

decreased tumor-free survival time ( J:197052 )

• due to pancreatic tumors

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Pten^tm1Rps/Pten^tm1Rps Tg(Tyr-cre/ERT2)13Bos/0
Genetic Background	involves: 129/Sv * 129S1/Sv * C57BL/6J * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Pten^tm1Rps mutation (0 available); any Pten mutation (86 available)
Tg(Tyr-cre/ERT2)13Bos mutation (11 available)

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

neoplasm

increased melanoma incidence ( J:155731 )

• following 4-hydroxytamoxifen (4-OHT) application, all mice develop melanoma over a 9 month period unlike wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
melanoma		DOID:1909		J:155731

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Kras^tm4Tyj/Kras⁺
Genetic Background	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Kras^tm4Tyj mutation (11 available); any Kras mutation (68 available)

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

mortality/aging

premature death ( J:124682 )

• mice inoculated with an adenovirus expressing cre recombinase (ad-cre) by inhalation have a median survival of 22 weeks after ad-cre inoculation

neoplasm

increased lung adenocarcinoma incidence ( J:124682 )

• mice inoculated with ad-cre by inhalation develop lung adenocarcinomas with high multiplicity, however metastasis is not observed

respiratory system

increased lung adenocarcinoma incidence ( J:124682 )

• mice inoculated with ad-cre by inhalation develop lung adenocarcinomas with high multiplicity, however metastasis is not observed

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Col1a1^{tm1(CAG-EGFR)Char}/Col1a1^{tm2(CAG-EGFR*)Char} Pten^tm1Hwu/Pten^tm1Hwu
Genetic Background	involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Col1a1^{tm1(CAG-EGFR)Char} mutation (0 available); any Col1a1 mutation (165 available)
Col1a1^{tm2(CAG-EGFR*)Char} mutation (0 available); any Col1a1 mutation (165 available)
Pten^tm1Hwu mutation (17 available); any Pten mutation (86 available)

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

mortality/aging

decreased tumor-free survival time ( J:146494 )

• no mice surviving tumor-free beyond 15 weeks following intracranial injection of an adenoviral cre unlike similarly treated Col1a1^{tm2(CAG-EGFR*)Char} or Col1a1^{tm1(CAG-EGFR)Char} homozygotes that do not develop tumors

neoplasm

increased glioblastoma incidence ( J:146494 )

• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 13 weeks unlike similarly treated Col1a1^{tm2(CAG-EGFR*)Char} or Col1a1^{tm1(CAG-EGFR)Char} homozygotes that do not develop tumors

nervous system

increased glioblastoma incidence ( J:146494 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
high grade glioma		DOID:3070	OMIM:PS137800	J:146494

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Col1a1^{tm1(CAG-EGFR)Char}/Col1a1^{tm1(CAG-EGFR)Char} Pten^tm1Hwu/Pten^tm1Hwu
Genetic Background	involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Col1a1^{tm1(CAG-EGFR)Char} mutation (0 available); any Col1a1 mutation (165 available)
Pten^tm1Hwu mutation (17 available); any Pten mutation (86 available)

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

mortality/aging

decreased tumor-free survival time ( J:146494 )

• 10% of mice die from glioblastoma multiforme development following intracranial injection of an adenoviral cre unlike similarly treated Col1a1^{tm1(CAG-EGFR)Char} homozygotes that do not develop tumors

neoplasm

increased glioblastoma incidence ( J:146494 )

• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with a greater than 90% tumor-free survival past 30 weeks unlike similarly treated Col1a1^{tm1(CAG-EGFR)Char} homozygotes that do not develop tumors

nervous system

increased glioblastoma incidence ( J:146494 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
high grade glioma		DOID:3070	OMIM:PS137800	J:146494

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Col1a1^{tm2(CAG-EGFR)Char}/Col1a1^{tm2(CAG-EGFR)Char} Pten^tm1Hwu/Pten^tm1Hwu
Genetic Background	involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Col1a1^{tm2(CAG-EGFR*)Char} mutation (0 available); any Col1a1 mutation (165 available)
Pten^tm1Hwu mutation (17 available); any Pten mutation (86 available)

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

mortality/aging

decreased tumor-free survival time ( J:146494 )

• no mice surviving tumor-free beyond 10 weeks following intracranial injection of an adenoviral cre unlike similarly treated Col1a1^{tm2(CAG-EGFR*)Char} homozygotes that do not develop tumors

neoplasm

increased glioblastoma incidence ( J:146494 )

• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 10 weeks unlike similarly treated Col1a1^{tm2(CAG-EGFR*)Char} homozygotes that do not develop tumors

nervous system

increased glioblastoma incidence ( J:146494 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
high grade glioma		DOID:3070	OMIM:PS137800	J:146494

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp E4f1^tm1Pisc/E4f1^tm1.1Llca Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a⁺
Genetic Background	involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
E4f1^tm1.1Llca mutation (2 available); any E4f1 mutation (38 available)
E4f1^tm1Pisc mutation (1 available); any E4f1 mutation (38 available)
Polr2a^{tm1(cre/ERT2)Bbd} mutation (3 available); any Polr2a mutation (92 available)

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

integument

hyperkeratosis ( J:167157 )

• development of hyperkeratosis following 4-hydroxytamoxifen treatment is reduced and delayed compared to mutant mice wild-type for Cdkn2a

epidermal hyperplasia ( J:167157 )

• development of hyperplasia following 4-hydroxytamoxifen treatment is reduced and delayed compared to mutant mice wild-type for Cdkn2a

abnormal keratinocyte physiology ( J:167157 )

• partial restoration in long term outgrowth of 4-hydroxytamoxifen exposed keratinocytes in culture compared to mutant mice wild-type for Cdkn2a

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Dicer1^tm1Snj/Dicer1^tm1Snj
Genetic Background	involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Dicer1^tm1Snj mutation (0 available); any Dicer1 mutation (96 available)

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

cellular

cellular phenotype ( J:139257 )

N	• mouse embryonic fibroblasts treated with an adenovirus cre exhibit normal cellular senescence

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp X/Tg(Tyr-HRAS)60Lc
Genetic Background	involves: 129/Sv * C57BL/6J * CBA/J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(Tyr-HRAS)60Lc mutation (0 available)

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

mortality/aging

decreased tumor-free survival time ( J:164588 )

• mice are euthanized within 20 weeks due to tumor development

neoplasm

decreased tumor growth/size ( J:164588 )

• tumor growth is less aggressive than in Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Kras^tm4Tyj/Kras⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Tyr-cre/ERT2)13Bos mice

increased melanoma incidence ( J:164588 )

• all mice develop melanomas within 20 weeks

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Ctnnb1^tm1Mmt/Ctnnb1^tm1Mmt Pten^tm1Rps/Pten^tm1Rps Tg(Tyr-cre/ERT2)13Bos/0
Genetic Background	involves: 129/Sv * C57BL/6J * FVB * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Ctnnb1^tm1Mmt mutation (0 available); any Ctnnb1 mutation (49 available)
Pten^tm1Rps mutation (0 available); any Pten mutation (86 available)
Tg(Tyr-cre/ERT2)13Bos mutation (11 available)

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

neoplasm

increased melanoma incidence ( J:155731 )

• following 4-hydroxytamoxifen (4-OHT) application, all mice develop melanoma over a 9 month period unlike wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
melanoma		DOID:1909		J:155731

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor⁺ Pten^tm1Rdp/Pten^tm1Rdp Tg(tetO-BRAF*V600E)29Lc/0 Tg(Tyr-cre/ERT2)13Bos/0
Genetic Background	involves: 129/Sv * C57BL/6J * FVB * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy} mutation (5 available); any Gt(ROSA)26Sor mutation (1034 available)
Pten^tm1Rdp mutation (0 available); any Pten mutation (86 available)
Tg(tetO-BRAF*V600E)29Lc mutation (0 available)
Tg(Tyr-cre/ERT2)13Bos mutation (11 available)

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

neoplasm

increased melanoma incidence ( J:221902 )

• tamoxifen treated mice administered doxycycline in the diet develop melanoma with a median latency of 60 days and with 85% penetrance

• withdrawal of doxycycline leads to rapid tumor regression

• treatment with PLX4720 BRAF inhibitor results in tumor growth inhibition in mutants, however, after continual administration of this inhibitor, mice develop drug resistance

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Fbxw11^tm1Nakay/Fbxw11^tm1Nakay
Genetic Background	B6.Cg-Cdkn2a^tm1Rdp Fbxw11^tm1Nakay

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Fbxw11^tm1Nakay mutation (0 available); any Fbxw11 mutation (72 available)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:228222 )

• phenotype is stated to be identical to that of Fbxw11^tm1Nakay homozygotes, indicating that concomitant inactivation of Cdkn2a does not rescue the lethal phenotype

embryo

embryonic growth arrest ( J:228222 )

embryonic growth retardation ( J:228222 )

growth/size/body

embryonic growth retardation ( J:228222 )

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(tetO-Nras*Q61K)#Lc/0 Tg(Tyr-rtTA)37Lc/0
Genetic Background	FVB.Cg-Cdkn2a^tm1Rdp Tg(tetO-Nras*Q61K)#Lc Tg(Tyr-rtTA)37Lc

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(tetO-Nras*Q61K)#Lc mutation (0 available)
Tg(Tyr-rtTA)37Lc mutation (0 available)

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

integument

increased cutaneous melanoma incidence ( J:238049 )

• mice administered doxycycline at weaning develop spontaneous melanoma after an average of 15 weeks with a 50% penetrance

• withdrawal of doxycycline results in rapid, durable and complete tumor regression within 10 days

• doxycycline treated mice administered the MEK inhibitor Selumetinib or GSK1120212 show tumor stasis but not tumor regression

• doxycycline treated mice administered a selective inhibitor of CDK4/6, PD-0332991 together with either Selumetinib or GSK1120212 show tumor regression

neoplasm

increased cutaneous melanoma incidence ( J:238049 )

• mice administered doxycycline at weaning develop spontaneous melanoma after an average of 15 weeks with a 50% penetrance

• withdrawal of doxycycline results in rapid, durable and complete tumor regression within 10 days

• doxycycline treated mice administered the MEK inhibitor Selumetinib or GSK1120212 show tumor stasis but not tumor regression

• doxycycline treated mice administered a selective inhibitor of CDK4/6, PD-0332991 together with either Selumetinib or GSK1120212 show tumor regression

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(GFAP-TVA)10Ech/0
Genetic Background	involves: 129 * BALB/c * C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(GFAP-TVA)10Ech mutation (0 available)

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

nervous system

increased glioma incidence ( J:52161 )

• 2 of 6 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR develop gliomas unlike similarly treated wild-type mice

hydrocephaly ( J:52161 )

• at 6 weeks, mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR develop hydrocephalus

neoplasm

increased glioma incidence ( J:52161 )

• 2 of 6 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR develop gliomas unlike similarly treated wild-type mice

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(NES-TVA)J12Ech/0
Genetic Background	involves: 129 * C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(NES-TVA)J12Ech mutation (1 available)

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

nervous system

increased glioma incidence ( J:52161 )

• 8 of 19 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR develop gliomas unlike similarly treated wild-type mice

• 4 of 10 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR and Cdk4 develop gliomas compared to 1 of 8 similarly treated wild-type mice

• 6 of 16 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR, Cdk4, and bFGF develop gliomas compared to 3 of 29 similarly treated wild-type mice

hydrocephaly ( J:52161 )

• in mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR and bFGF or Cdk4

neoplasm

increased glioma incidence ( J:52161 )

• 8 of 19 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR develop gliomas unlike similarly treated wild-type mice

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a⁺ Tg(NES-TVA)J12Ech/0
Genetic Background	involves: 129 * C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(NES-TVA)J12Ech mutation (1 available)

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

neoplasm

increased glioma incidence ( J:52161 )

• 13 of 25 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR develop gliomas unlike similarly treated wild-type mice

nervous system

increased glioma incidence ( J:52161 )

• 13 of 25 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR develop gliomas unlike similarly treated wild-type mice

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-Kras2)12Hev/0
Genetic Background	involves: 129 * C57BL/6J * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(Scgb1a1-rtTA)1Jaw mutation (3 available)
Tg(tetO-Kras2)12Hev mutation (2 available)

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

neoplasm

increased lung tumor incidence ( J:73468 )

• doxycycline-treated mice initiate lung tumors more rapidly than in Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice with a more malignant phenotype

• however, tumors regress after doxycycline withdrawal due to apoptosis

increased lung adenocarcinoma incidence ( J:73468 , J:166963 )

• more sooner in doxycycline-treated mice compared with Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice (J:73468)

• in doxycycline-treated mice (J:166963)

respiratory system

increased lung tumor incidence ( J:73468 )

• doxycycline-treated mice initiate lung tumors more rapidly than in Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice with a more malignant phenotype

• however, tumors regress after doxycycline withdrawal due to apoptosis

increased lung adenocarcinoma incidence ( J:73468 , J:166963 )

• more sooner in doxycycline-treated mice compared with Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice (J:73468)

• in doxycycline-treated mice (J:166963)

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Rnf2^tm1Mvl/Rnf2^tm1Mvl
Genetic Background	involves: 129P2/Ola * 129/Sv * C57BL/6J * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Rnf2^tm1Mvl mutation (0 available); any Rnf2 mutation (34 available)

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

embryo

embryonic growth arrest ( J:82399 )

• development does not progress past E11-E12

abnormal somite development ( J:82399 )

• some somites are laid down in paraxial mesoderm which is never observed in Rnf2 homozygotes

nervous system

abnormal forebrain development ( J:82399 )

• abnormal forebrain development with a near complete lack of head mesenchyme

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Sox10^tm1Weg/Sox10⁺ Tg(Tyr-NRAS*Q61K)1Bee/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Sox10^tm1Weg mutation (1 available); any Sox10 mutation (32 available)
Tg(Tyr-NRAS*Q61K)1Bee mutation (1 available)

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

pigmentation

pigmentation phenotype ( J:193443 )

N	• loss of the hyperpigmentation that is seen in Cdkn2a^tm1Rdp/ Cdkn2a^tm1Rdp Tg(Tyr-NRAS*Q61K)1Bee/0 mice resulting in an almost normal pigmentation pattern

neoplasm

neoplasm ( J:193443 )

N	• no signs of primary melanoma formation are seen at 6 months of age

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a⁺ Nf1^tm1Tyj/Nf1⁺
Genetic Background	involves: 129S2/SvPas * 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Nf1^tm1Tyj mutation (3 available); any Nf1 mutation (158 available)

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

neoplasm

increased neurofibrosarcoma incidence ( J:131914 )

• seen at lower frequencies and greater age (over 1 year) compared to mice heterozygous for Nf1^tm1Tyj and homozygous for Cdkn2a^tm2Rdp

nervous system

increased neurofibrosarcoma incidence ( J:131914 )

• seen at lower frequencies and greater age (over 1 year) compared to mice heterozygous for Nf1^tm1Tyj and homozygous for Cdkn2a^tm2Rdp

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Nf1^tm1Tyj/Nf1⁺
Genetic Background	involves: 129S2/SvPas * 129S6/SvEvTac

Find Mice

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

mortality/aging

premature death ( J:131914 )

• virtually all mice die by 10 months of age

neoplasm

increased leukemia incidence ( J:131914 )

• seen in some mice

increased lymphoma incidence ( J:131914 )

• significant frequency of hematopoietic neoplasms consisting mainly of lymphomas and histiocytic neoplasms with lower incidences of acute myeloid leukemias and myeloproliferative disease

increased neurofibrosarcoma incidence ( J:131914 )

• developed in 26% of mice

• in most cases these tumors are grossly evident by 4 to 6 months of age

nervous system

nervous system phenotype ( J:131914 )

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

increased neurofibrosarcoma incidence ( J:131914 )

• developed in 26% of mice

• in most cases these tumors are grossly evident by 4 to 6 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant peripheral nerve sheath tumor		DOID:5940		J:131914

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp
Genetic Background	involves: 129/Sv * 129S2/SvPas * C57BL/6 * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (61 available)
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)

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

cellular

abnormal cell physiology ( J:72780 )

• vHaras-induced foci formation in primary keratinocytes is increased compared with similarly treated wild-type and single homozygous cells indicating increased tumorgenicity

increased keratinocyte proliferation ( J:72780 )

• keratinocyte proliferation is increased compared to in wild-type cells

delayed cellular replicative senescence ( J:72780 )

• age-related senescence in the epidermis in vivo is almost absent compared to in wild-type mice

• vHaras-induced premature senescence of primary keratinocytes is decreased compared with similarly treated wild-type cells

• however, calcium- and Tgfb-induced cell growth arrest is normal

neoplasm

increased squamous cell carcinoma incidence ( J:72780 )

• 2 tumors are observed when keratinocytes are transplanted into nude mice unlike when wild-type cells are used

• all nude mice transplanted with keratinocytes infected with a vHaras-expressing retrovirus develop poorly differentiated SCCs with spindle cell morphology unlike nude mice receiving similarly treated wild-type cells

integument

abnormal skin development ( J:72780 )

• mice exhibit altered expression of several markers of epidermis differentiation compared with wild-type mice

abnormal skin physiology ( J:72780 )

• age-related senescence in the epidermis in vivo is almost absent compared to in wild-type mice

abnormal keratinocyte physiology ( J:72780 )

• as determined by marker expression, in vitro keratinocyte differentiation is altered compared with similarly treated cells from wild-type mice and single homozygotes

• vHaras-induced premature senescence of primary keratinocytes is decreased while foci formation is increased compared with similarly treated wild-type cells and single homozygous

• however, calcium- and Tgfb-induced cell growth arrest is normal

increased keratinocyte proliferation ( J:72780 )

• keratinocyte proliferation is increased compared to in wild-type cells

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Lig4^tm1Fwa/Lig4^tm1Fwa
Genetic Background	involves: 129/Sv * 129S6/SvEvTac * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Lig4^tm1Fwa mutation (2 available); any Lig4 mutation (46 available)

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

mortality/aging

prenatal lethality, complete penetrance ( J:63078 )

• no doubly-deficient offspring are observed (0/170)

• numbers of double heterozygotes observed are similar to expected numbers

cellular

decreased cell proliferation ( J:63078 )

• MEFs show premature growth arrest compared to wild-type MEFs

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a⁺ Lig4^tm1Fwa/Lig4^tm1Fwa
Genetic Background	involves: 129/Sv * 129S6/SvEvTac * C57BL/6J * SJL

Find Mice

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

mortality/aging

prenatal lethality, complete penetrance ( J:63078 )

• no doubly-deficient offspring are observed (0/170)

• numbers of double heterozygotes observed are similar to expected numbers

cellular

increased cellular sensitivity to ionizing radiation ( J:63078 )

• cells are highly sensitive to ionizing radiation compared to wild-type or Cdkn2a-deficient MEFs

increased neuron apoptosis ( J:63078 )

• high levels of pyknotic cells are observed in doubly-deficient embryos

decreased cell proliferation ( J:63078 )

• MEFs show premature growth arrest compared to wild-type MEFs

nervous system

increased neuron apoptosis ( J:63078 )

• high levels of pyknotic cells are observed in doubly-deficient embryos

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Dicer1^tm1Snj/Dicer1^tm1Snj
Genetic Background	involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * SJL

Find Mice

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

cellular

increased cell proliferation ( J:139257 )

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(GFAP-TVA)5Hev/0
Genetic Background	involves: 129/Sv * BALB/c * C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(GFAP-TVA)5Hev mutation (1 available)

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

mortality/aging

premature death ( J:125535 )

• after 84 days, mice transfected with replication-competent ALV splice acceptor viral vector expressing PDGFB exhibit 30% compared to 85% survival in similarly treated Tg(GFAP-TVA)5Hev mice

neoplasm

increased glioma incidence ( J:125535 )

• 19 gliomas are discovered in 28 mice transfected with replication-competent ALV splice acceptor viral vector expressing PDGFB

increased oligodendroglioma incidence ( J:125535 )

• 5 grade II (similar to human oligodendroglioma) and 14 grade III (similar to anaplastic oligodendroglioma) tumors were found

nervous system

increased glioma incidence ( J:125535 )

• 19 gliomas are discovered in 28 mice transfected with replication-competent ALV splice acceptor viral vector expressing PDGFB

increased oligodendroglioma incidence ( J:125535 )

• 5 grade II (similar to human oligodendroglioma) and 14 grade III (similar to anaplastic oligodendroglioma) tumors were found

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-NRAS*Q61K)1Bee/?
Genetic Background	involves: 129/Sv * C57BL/6 * DBA/2 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(Tyr-NRAS*Q61K)1Bee mutation (1 available)

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

neoplasm

increased cutaneous melanoma incidence ( J:98545 )

• 17 of 18 mice develop cutaneous melanomas within 6 months of birth

• melanomas present as black and frequently ulcerated nodules that are found in the trunk (in 81% of mice), upper and lower extremities (in 22% of mice), and head and neck (in 39% of mice)

• acral melanomas and melanomas of the genitalia are present in a few mice

• melanomas are predominantly melanotic and epitheloid containing numerous macrophages and are vascularized

• in some tumors, atypical melanocytes are found un the surface or adnexal epithelium

• in some mice tumors are present within a rather hyperplastic epidermis or at the epidermal/dermal junction of hair follicle

• only 10% to 50% of tumor cells express nestin indicating that melanomas are comprised of at least two subpopulations

increased metastatic potential ( J:98545 )

• melanomas metastasize to the liver and lung in 36% of mice

immune system

enlarged lymph nodes ( J:98545 )

• 64% of tumor-bearing mice exhibit enlarged lymph nodes

integument

increased cutaneous melanoma incidence ( J:98545 )

• 17 of 18 mice develop cutaneous melanomas within 6 months of birth

• melanomas present as black and frequently ulcerated nodules that are found in the trunk (in 81% of mice), upper and lower extremities (in 22% of mice), and head and neck (in 39% of mice)

• acral melanomas and melanomas of the genitalia are present in a few mice

• melanomas are predominantly melanotic and epitheloid containing numerous macrophages and are vascularized

• in some tumors, atypical melanocytes are found un the surface or adnexal epithelium

• in some mice tumors are present within a rather hyperplastic epidermis or at the epidermal/dermal junction of hair follicle

• only 10% to 50% of tumor cells express nestin indicating that melanomas are comprised of at least two subpopulations

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
skin melanoma		DOID:8923	OMIM:608035 OMIM:612263	J:98545

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a⁺ Tg(Tyr-NRAS*Q61K)1Bee/?
Genetic Background	involves: 129/Sv * C57BL/6 * DBA/2 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(Tyr-NRAS*Q61K)1Bee mutation (1 available)

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

neoplasm

increased cutaneous melanoma incidence ( J:98545 )

• 15 of 18 mice develop cutaneous melanomas within 12 months of birth

integument

increased cutaneous melanoma incidence ( J:98545 )

• 15 of 18 mice develop cutaneous melanomas within 12 months of birth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
skin melanoma		DOID:8923	OMIM:608035 OMIM:612263	J:98545

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(NES-TVA)J12Ech/0
Genetic Background	involves: 129/Sv * C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(NES-TVA)J12Ech mutation (1 available)

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

mortality/aging

premature death ( J:125535 , J:153220 )

• after 84 days, mice transfected with replication-competent ALV splice acceptor viral vector expressing PDGFB exhibit 15% compared to 50% survival in similarly treated Tg(NES-TVA)12Hev mice (J:125535)

• co delivery of RCAS-PDGFB and an antisense construct targeting Igfbp2 results in improved survival compared to mice infected with RCAS-PDGFB alone (J:153220)

neoplasm

increased glioma incidence ( J:125535 )

• 17 gliomas are discovered in 20 mice transfected with replication-competent ALV splice acceptor viral vector expressing PDGFB

• 6 grade II (similar to human oligodendroglioma) and 11 grade III (similar to anaplastic oligodendroglioma)

increased oligodendroglioma incidence ( J:153220 )

• infection with RCAS-PDGFB induces anaplastic oligodendrogliomas in 97% of mice

• tumors are highly aggressive and display multiple foci of pseudopalisading necrosis and microvascular proliferation

• co-infection with RCAS-PDGFB and RCAS-IGFBP2 results in tumors that are histopathologically identical to those in mice infected with only RCAS-PDGFB

• co delivery of RCAS-PDGFB and an antisense construct targeting Igfbp2 results in a primarily anaplastic oligodendrogliomas but 18% of tumors are lower grade oligodendrogliomas

nervous system

increased glioma incidence ( J:125535 )

• 17 gliomas are discovered in 20 mice transfected with replication-competent ALV splice acceptor viral vector expressing PDGFB

• 6 grade II (similar to human oligodendroglioma) and 11 grade III (similar to anaplastic oligodendroglioma)

increased oligodendroglioma incidence ( J:153220 )

• infection with RCAS-PDGFB induces anaplastic oligodendrogliomas in 97% of mice

• tumors are highly aggressive and display multiple foci of pseudopalisading necrosis and microvascular proliferation

• co-infection with RCAS-PDGFB and RCAS-IGFBP2 results in tumors that are histopathologically identical to those in mice infected with only RCAS-PDGFB

• co delivery of RCAS-PDGFB and an antisense construct targeting Igfbp2 results in a primarily anaplastic oligodendrogliomas but 18% of tumors are lower grade oligodendrogliomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
oligodendroglioma		DOID:3181		J:153220

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a⁺ X/Tg(Tyr-HRAS)60Lc
Genetic Background	involves: 129/Sv * C57BL/6J * CBA/J * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(Tyr-HRAS)60Lc mutation (0 available)

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

neoplasm

increased intraocular melanoma incidence ( J:140820 )

• following exposure to UVA and UVB, 2 of 46 mice exhibit uveal melanoma

increased incidence of tumors by UV-induction ( J:140820 )

• following exposure to UVA and UVB, 2 of 46 mice exhibit uveal melanoma

vision/eye

increased intraocular melanoma incidence ( J:140820 )

• following exposure to UVA and UVB, 2 of 46 mice exhibit uveal melanoma

cataract ( J:140820 )

• following exposure to UVA and UVB, only one mouse developed cataracts unlike Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-HRAS)60Lc mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
uveal melanoma		DOID:6039	OMIM:155720 OMIM:606660 OMIM:606661	J:140820

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-BRAF*V600E)470Fgh/0
Genetic Background	involves: 129/Sv * C57BL/6J * CBA * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(Tyr-BRAF*V600E)470Fgh mutation (0 available)

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

mortality/aging

premature death ( J:151455 )

• survival is less than in Tg(Tyr-BRAF*V600E)470Fgh mice dying within days or weeks of developing hydrocephalus and paralysis

neoplasm

increased melanoma incidence ( J:151455 )

• mice develop increased incidence of melanomas with reduced latency and decreased lifespan compared to mice with Tg(Tyr-BRAF*V600E)470Fgh

• mice exhibit metastasis to the lung and lymph nodes

behavior/neurological

paralysis ( J:151455 )

nervous system

hydrocephaly ( J:151455 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
melanoma		DOID:1909		J:151455

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-BRAF*V600E)476Fgh/0
Genetic Background	involves: 129/Sv * C57BL/6J * CBA * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(Tyr-BRAF*V600E)476Fgh mutation (0 available)

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

mortality/aging

premature death ( J:151455 )

• survival is less than in Tg(Tyr-BRAF*V600E)470Fgh mice

neoplasm

increased melanoma incidence ( J:151455 )

• mice develop increased incidence of melanomas with reduced latency and decreased lifespan compared to mice with Tg(Tyr-BRAF*V600E)476Fgh

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
melanoma		DOID:1909		J:151455

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(S100b-v-erbB)4496Waw/0
Genetic Background	involves: 129/Sv * C57BL/6J * DBA/2J * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(S100b-v-erbB)4496Waw mutation (0 available)

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

mortality/aging

premature death ( J:82649 )

• 75% of mice die by 2 months of age and 90% of mice are dead by 6 months due to development of oligodendroglioma

neoplasm

increased glioma incidence ( J:82649 )

• mice exhibit increased penetrance of glioma development compared to Tg(S100b-v-erbB)4496Waw mice

increased oligodendroglioma incidence ( J:82649 )

• 75% of mice die by 2 months of age and 90% of mice are dead by 6 months due to development of oligodendroglioma

decreased tumor latency ( J:82649 )

• mice exhibit decreased latency of glioma development compared to Tg(S100b-v-erbB)4496Waw mice

nervous system

increased glioma incidence ( J:82649 )

• mice exhibit increased penetrance of glioma development compared to Tg(S100b-v-erbB)4496Waw mice

increased oligodendroglioma incidence ( J:82649 )

• 75% of mice die by 2 months of age and 90% of mice are dead by 6 months due to development of oligodendroglioma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
oligodendroglioma		DOID:3181		J:82649

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a⁺ Tg(S100b-v-erbB)4496Waw/0
Genetic Background	involves: 129/Sv * C57BL/6J * DBA/2J * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(S100b-v-erbB)4496Waw mutation (0 available)

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

neoplasm

increased glioma incidence ( J:82649 )

• mice develop gliomas as in Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(S100b-v-erbB)4496Waw mice with loss of function of the wild-type Cdkn2a allele

nervous system

increased glioma incidence ( J:82649 )

• mice develop gliomas as in Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(S100b-v-erbB)4496Waw mice with loss of function of the wild-type Cdkn2a allele

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
oligodendroglioma		DOID:3181		J:82649

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-NRAS*Q61K)1Bee/0
Genetic Background	involves: 129/Sv * C57BL/6J * DBA/2 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(Tyr-NRAS*Q61K)1Bee mutation (1 available)

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

integument

skin lesions ( J:193443 )

• dermal lesions that resemble giant congenital naevi

increased cutaneous melanoma incidence ( J:193443 )

• 100% of mutants develop melanoma by 6 months of age

pigmentation

hyperpigmentation ( J:193443 )

• hyperpigmentation of the naevus nests close to the epidermis and naevus cells around and within hair follicles and other adnexal structures such as sebaceous glands

• skin hyperpigmentation is apparent at the first postnatal week and is restricted to the dermis

neoplasm

increased cutaneous melanoma incidence ( J:193443 )

• 100% of mutants develop melanoma by 6 months of age

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Mt1-Hgf)19Lmb/0
Genetic Background	involves: 129/Sv * C57BL/6J * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(Mt1-Hgf)19Lmb mutation (1 available)

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

neoplasm

increased tumor incidence ( J:79704 )

• alpha-actin positive neoplasms arise also at ectopic non-skeletal muscle sites, such as cerebellum, pituitary, esophagus, pancreas and stomach

increased rhabdomyosarcoma incidence ( J:79704 )

• mutants develop malignant rhabdomyosarcoma arising from trunk and limb skeletal muscle with high penetrance and short latency

• mean age of onset of 3.3 months

increased melanoma incidence ( J:79704 )

• 2 of 34 mutants develop malignant melanoma

muscle

abnormal myogenesis ( J:79704 )

• myogenic precursors (satellite cells) cultured in fusion media remain poorly differentiated, indicating blocked myogenesis

increased satellite cell number ( J:79704 )

• earlier appearance of hyperplastic satellite cells in skeletal muscle

increased rhabdomyosarcoma incidence ( J:79704 )

• mutants develop malignant rhabdomyosarcoma arising from trunk and limb skeletal muscle with high penetrance and short latency

• mean age of onset of 3.3 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rhabdomyosarcoma		DOID:3247		J:79704

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a⁺ Terc^tm1Rdp/Terc^tm1Rdp
Genetic Background	involves: 129/Sv * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Terc^tm1Rdp mutation (4 available); any Terc mutation (8 available)

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

neoplasm

increased tumor incidence ( J:120065 )

• 84% of early generation mutants succumb to tumors with a median tumor-free latency of 71.6 weeks

• late generation mutants show a decrease in percent tumor death and an increase in tumor-free latency, from 84% to 20% and 71.6-104.9 weeks

increased lymphoma incidence ( J:120065 )

• 19% and 23% of early generation and late generation mutants, respectively, develop lymphomas

increased sarcoma incidence ( J:120065 )

• 35% and 39% of early generation and late generation mutants, respectively, develop histocytic sarcomas

• 20% and 23% of early generation and late generation mutants, respectively, develop soft tissue sarcomas

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(tetO-BRAF*V600E)29Lc/0 Tg(Tyr-rtTA)37Lc/0
Genetic Background	involves: 129/Sv * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Tg(tetO-BRAF*V600E)29Lc mutation (0 available)
Tg(Tyr-rtTA)37Lc mutation (0 available)

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

mortality/aging

premature death ( J:144358 )

• 50% of doxycycline-treated mice die due to generally compromised physiological state secondary to renal failure despite frequent bladder irrigations

neoplasm

increased prostate gland adenocarcinoma incidence ( J:144358 )

• at 24 weeks after doxycycline induction, mice develop prostate adenocarcinomas that exhibit epithelial-mesenchyme transition

• doxycycline-induced prostate adenomas can compress the bladder, originate from epithelial cells and express luminal, intermediate and basal cell markers

• doxycycline-treated mice that are subsequently castrated exhibit reduced prostate tumor proliferation compared to pre-castration

• withdrawal of doxycycline does not affect tumor cell proliferation

endocrine/exocrine glands

prostate gland hyperplasia ( J:144358 )

• at 16 weeks after doxycycline induction, prostates exhibit basaloid hyperplasia driven by urogenital epithelium unlike in wild-type mice

increased prostate gland adenocarcinoma incidence ( J:144358 )

• at 24 weeks after doxycycline induction, mice develop prostate adenocarcinomas that exhibit epithelial-mesenchyme transition

• doxycycline-induced prostate adenomas can compress the bladder, originate from epithelial cells and express luminal, intermediate and basal cell markers

• doxycycline-treated mice that are subsequently castrated exhibit reduced prostate tumor proliferation compared to pre-castration

• withdrawal of doxycycline does not affect tumor cell proliferation

abnormal prostate gland physiology ( J:144358 )

• at 5 weeks after doxycycline induction, prostates exhibit a moderate degree of aberrant proliferation unlike in wild-type mice

reproductive system

prostate gland hyperplasia ( J:144358 )

• at 16 weeks after doxycycline induction, prostates exhibit basaloid hyperplasia driven by urogenital epithelium unlike in wild-type mice

increased prostate gland adenocarcinoma incidence ( J:144358 )

• at 24 weeks after doxycycline induction, mice develop prostate adenocarcinomas that exhibit epithelial-mesenchyme transition

• doxycycline-induced prostate adenomas can compress the bladder, originate from epithelial cells and express luminal, intermediate and basal cell markers

• doxycycline-treated mice that are subsequently castrated exhibit reduced prostate tumor proliferation compared to pre-castration

• withdrawal of doxycycline does not affect tumor cell proliferation

abnormal prostate gland physiology ( J:144358 )

• at 5 weeks after doxycycline induction, prostates exhibit a moderate degree of aberrant proliferation unlike in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:144358

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Mxi1^tm1Rdp/Mxi1^tm1Rdp
Genetic Background	involves: 129/Sv * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)
Mxi1^tm1Rdp mutation (0 available); any Mxi1 mutation (34 available)

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

neoplasm

increased tumor incidence ( J:48236 )

• over an observation period of 30 weeks, 80% of Cdkn2a^tm1Rdp mice versus only 44% of double homozygous mutant mice survived and remained tumor-free

• the spectrum of tumor types detected in double homozygous mutant mice was similar to that observed in Cdkn2a^tm1Rdp mice alone (the predominant tumor types being fibrosarcoma and lymphoma)

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Terc^tm1Rdp/Terc^tm1Rdp
Genetic Background	involves: 129/Sv * C57BL/6J * SJL

Find Mice

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

Degenerative phenotypes, including increased apoptosis in gastrointestinal crypts and germ cell depletion, in Terc^tm1Rdp/Terc^tm1Rdp and Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Terc^tm1Rdp/Terc^tm1Rdp mice

mortality/aging

premature aging ( J:120065 )

• 12- to 13-week old late generation (G4) mutants exhibit accelerated degeneration as indicated by hair graying, alopecia, kyphosis, reduced body size and weight, and fragility

neoplasm

increased tumor incidence ( J:120065 )

• 98% of early generation mutants succumb to tumors with a median tumor-free latency of 38.6 weeks

• late generation mutants show a decrease in percent tumor death and an increase in tumor-free latency, from 98% to 43% and 38.6-65.3 weeks compared to early generation mutants

increased lymphoma incidence ( J:120065 )

• 11% and 10% of early generation and late generation mutants, respectively, develop lymphomas

increased sarcoma incidence ( J:120065 )

• 57% and 59% of early generation and late generation mutants, respectively, develop histocytic sarcomas

• 24% and 28% of early generation and late generation mutants, respectively, develop soft tissue sarcomas

cellular

abnormal telomere length ( J:120065 )

• the anaphase bridge index (ABI) is increased to the same extent as in Terc^tm1Rdp homozygotes in late-generation (G4/G5) intestinal crypts indicating telomere dysfunction

increased male germ cell apoptosis ( J:120065 )

• apoptotic depletion of germ cells in late generation mutants

decreased cell proliferation ( J:120065 )

• MEFs grown in culture show decreased growth rates after 10 population doublings with steady slow proliferation thereafter, indicating that telomere dysfunction suppresses the growth rate

• early generation (G0) astrocytes show continuous proliferation whereas the late generation (G4) astrocytes senesce after 2.5 population doublings, indicating that telomere dysfunction constrains the immortalization potential of astrocytes

reproductive system

increased male germ cell apoptosis ( J:120065 )

• apoptotic depletion of germ cells in late generation mutants

testicular atrophy ( J:120065 )

• testicular atrophy and associated apoptotic depletion of germ cells in late generation mutants

growth/size/body

decreased body size ( J:120065 )

• late generation mutants have reduced body size and are fragile

decreased body weight ( J:120065 )

• late generation mutants have reduced body weight

digestive/alimentary system

abnormal intestine morphology ( J:120065 )

• the GI crypts of late generation mutants exhibit high levels of apoptosis

skeleton

kyphosis ( J:120065 )

• late generation mutants exhibit kyphosis

endocrine/exocrine glands

testicular atrophy ( J:120065 )

• testicular atrophy and associated apoptotic depletion of germ cells in late generation mutants

Allelic Composition	Cav1^tm1Mls/Cav1^tm1Mls Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp
Genetic Background	involves: 129/Sv * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cav1^tm1Mls mutation (2 available); any Cav1 mutation (32 available)
Cdkn2a^tm1Rdp mutation (3 available); any Cdkn2a mutation (58 available)

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

cellular

abnormal cell cycle ( J:90334 )

• MEFs exhibit an increase in the S-phase fraction and a decrease in the G0/G1 fraction, indicating an arrest in the G0/G1 phase

increased fibroblast proliferation ( J:90334 )

• MEFs exhibit increased hyperproliferation compared to single Cdkn2a homozygous MEFs

endocrine/exocrine glands

abnormal mammary gland duct morphology ( J:90334 )

• fibrosis of the mammary gland epithelial duct

• increase in ductal wall thickness

abnormal branching of the mammary ductal tree ( J:90334 )

• increase in side-branching of the mammary gland epithelial duct

mammary gland duct hyperplasia ( J:90334 )

• hyperplasia of the mammary gland epithelial duct

integument

abnormal mammary gland duct morphology ( J:90334 )

• fibrosis of the mammary gland epithelial duct

• increase in ductal wall thickness

abnormal branching of the mammary ductal tree ( J:90334 )

• increase in side-branching of the mammary gland epithelial duct

mammary gland duct hyperplasia ( J:90334 )

• hyperplasia of the mammary gland epithelial duct

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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