Phenotypes associated with this allele

• Allele Symbol: Jun^tm4Wag
• Allele Name: targeted mutation 4, Erwin F Wagner
• Allele ID: MGI:2445420
• Summary: 15 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Jun^tm4Wag/Jun^tm4Wag Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd	MGI:5293752
cn2	Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Jun^tm2.1Wag/Jun^tm4Wag Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5293753
cn3	Jun^tm4Wag/Jun^tm4Wag Isl1^tm1(cre)Sev/Isl1^+	involves: 129P2/OlaHsd * 129S/Sv	MGI:7562242
cn4	Jun^tm1Pa/Jun^tm4Wag Isl1^tm1(cre)Sev/Isl1^+	involves: 129P2/OlaHsd * 129S/Sv * 129X1/SvJ * C57BL/6J	MGI:7562004
cn5	Jun^tm1Pa/Jun^tm4Wag Tg(Tek-cre)1Ywa/0	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * C57BL/6J * SJL	MGI:7562249
cn6	Jun^tm4Wag/Jun^tm4Wag Tg(Nes-cre)1Wme/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:2451283
cn7	Jun^tm4Wag/Jun^tm4Wag Tg(COL2A1-cre)1Wag/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:2451284
cn8	Jun^tm4Wag/Jun^tm4Wag Tg(Mx1-cre)1Cgn/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:2451303
cn9	Jun^tm4Wag/Jun^tm4Wag Tg(Sftpc-cre)1Blh/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5306592
cn10	Jun^tm4Wag/Jun^tm4Wag Tg(Nes-cre)1Kln/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5294554
cn11	Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Jun^tm4Wag/Jun^+ Tg(Nes-cre)1Kln/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:4867644
cn12	Jun^tm4Wag/Jun^tm4Wag Junb^tm3Wag/Junb^tm3Wag Tg(Krt1-5-cre/ERT)1Ipc/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5578332
cn13	Jun^tm4Wag/Jun^tm4Wag Tg(Tek-cre)1Ywa/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:7562246
cn14	Jun^tm4Wag/Jun^tm4Wag Tg(Alb1-cre)7Gsc/0	involves: 129P2/OlaHsd * FVB/N	MGI:2451292
cn15	Isl1^tm1(cre)Sev/Isl1^+ Jun^tm4Wag/Jun^+	Not Specified	MGI:7562245

Genotype
MGI:5293752

cn1

• Allelic Composition: Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe; Jun^tm4Wag/Jun^tm4Wag; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd

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

nervous system

abnormal Purkinje cell morphology ( J:176598 )

• Purkinje cells exhibit partial rescue of organization and arborization compared with Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Tg(En2-cre)22Alj mice

• however, Purkinje cell density is rescued

abnormal cerebellum fissure morphology ( J:176598 )

• supranumeral fissures

small cerebellum ( J:176598 )

• partially rescued compared with Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Tg(En2-cre)22Alj mice

Genotype
MGI:5293753

cn2

• Allelic Composition: Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe; Jun^tm2.1Wag/Jun^tm4Wag; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

nervous system

abnormal Purkinje cell morphology ( J:176598 )

• Purkinje cells exhibit partial rescue of organization and arborization compared with Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Tg(En2-cre)22Alj mice

• however, Purkinje cell density is rescued

small cerebellum ( J:176598 )

Genotype
MGI:7562242

cn3

• Allelic Composition: Jun^tm4Wag/Jun^tm4Wag; Isl1^tm1(cre)Sev/Isl1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S/Sv

mortality/aging

mortality/aging ( J:199412 )

N • mice are present at the expected Mendelian ratios at E14.5-P0, indicating normal embryonic survival

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:199412 )

• at E14.5 to P0, seven of 22 (32%) embryos exhibit aortic arch artery remodeling defects, including interrupted aortic arch (IAA) type B, hypoplasia of the B segment of the aortic arch, and aberrant retro-esophageal right subclavian artery

retroesophageal right subclavian artery ( J:199412 )

• at E14.5 to P0, seven of 22 (32%) embryos exhibit aberrant retro-esophageal right subclavian artery

interrupted aortic arch, type b ( J:199412 )

• at E14.5 to P0, seven of 22 (32%) embryos exhibit interrupted aortic arch (IAA) type B

abnormal cardiac outflow tract development ( J:199412 )

• at E14.5 to P0, seven of 8 (88%) embryos exhibit outflow tract (OFT) defects, including ventricular septal defect (VSD), double outlet right ventricle, and semilunar valve hyperplasia

• a non-significant trend toward a decrease in proliferating pHH3+ cells and an increase in apoptotic TUNEL+ cells is noted in the OFT at E10.5

double outlet right ventricle ( J:199412 )

• at E14.5 to P0, seven of 8 (88%) embryos exhibit DORV

ventricular septal defect ( J:199412 )

• at E14.5 to P0, seven of 8 (88%) embryos exhibit VSDs

abnormal aortic valve morphology ( J:199412 )

• at E14.5 to P0, six of 8 (75%) embryos exhibit an aortic valve defect

abnormal pulmonary valve morphology ( J:199412 )

• at E14.5 to P0, seven of 8 (88%) embryos exhibit a pulmonary valve defect

abnormal pulmonary valve cusp morphology ( J:199412 )

• at PO, pulmonary valve leaflets are enlarged and hyperplastic

semilunar valve hyperplasia ( J:199412 )

• at E14.5 to P0, seven of 8 (88%) embryos exhibit semilunar valve hyperplasia

• however, atrioventricular (mitral and tricuspid) valves are unaffected

embryo

abnormal pharyngeal arch artery morphology ( J:199412 )

• at E14.5 to P0, seven of 22 (32%) embryos exhibit aortic arch artery remodeling defects, including interrupted aortic arch (IAA) type B, hypoplasia of the B segment of the aortic arch, and aberrant retro-esophageal right subclavian artery

craniofacial

abnormal pharyngeal arch artery morphology ( J:199412 )

• at E14.5 to P0, seven of 22 (32%) embryos exhibit aortic arch artery remodeling defects, including interrupted aortic arch (IAA) type B, hypoplasia of the B segment of the aortic arch, and aberrant retro-esophageal right subclavian artery

Genotype
MGI:7562004

cn4

• Allelic Composition: Jun^tm1Pa/Jun^tm4Wag; Isl1^tm1(cre)Sev/Isl1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system

cardiovascular system phenotype ( J:199412 )

N • at E10.5, embryos show normal expression of Nfatc1 (an endocardial marker) relative to controls, suggesting normal endocardial formation

N • a non-significant trend toward a decrease in proliferating pHH3+ cells and an increase in apoptotic TUNEL+ cells is noted in the cardiac outflow tract (OFT) at E10.5

embryo

embryo phenotype ( J:199412 )

N • at E10.5, embryos show normal expression of Tfap2a during cardiac OFT development relative to controls, suggesting normal cardiac neural crest cell migration

Genotype
MGI:7562249

cn5

• Allelic Composition: Jun^tm1Pa/Jun^tm4Wag; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * C57BL/6J * SJL

embryo

embryo phenotype ( J:199412 )

N • at E10.5, embryos show a similar pattern of Tfap2a expression in the developing cardiac outflow tract (OFT) and pharyngeal arches relative to controls, suggesting normal cardiac neural crest cell migration

Genotype
MGI:2451283

cn6

• Allelic Composition: Jun^tm4Wag/Jun^tm4Wag; Tg(Nes-cre)1Wme/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

mortality/aging

postnatal lethality, incomplete penetrance ( J:80022 )

• 2% of animals survive to weaning

prenatal lethality, incomplete penetrance ( J:80022 )

• animals born at less than the predicted Mendelian ratio

growth/size/body

decreased body size ( J:80022 )

decreased body length ( J:80022 )

• short body axis

skeleton

kyphosis ( J:80022 )

scoliosis ( J:80022 )

fusion of vertebral arches ( J:80022 )

• fusion of neural arches

vision/eye

eyelids open at birth ( J:80022 )

• severity of phenotype was variable

Genotype
MGI:2451284

cn7

• Allelic Composition: Jun^tm4Wag/Jun^tm4Wag; Tg(COL2A1-cre)1Wag/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

skeleton

abnormal thoracic cage morphology ( J:80022 )

scoliosis ( J:80022 )

Genotype
MGI:2451303

cn8

• Allelic Composition: Jun^tm4Wag/Jun^tm4Wag; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

liver/biliary system

abnormal liver regeneration ( J:75863 )

• following induction with IFN or pI-pC and 70% partial hepatectomy, abnormal architecture, hepatocyte death, and accumulation of cytoplasmic fat droplets were observed in the regenerating liver

Genotype
MGI:5306592

cn9

• Allelic Composition: Jun^tm4Wag/Jun^tm4Wag; Tg(Sftpc-cre)1Blh/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

cellular

increased lung apoptosis ( J:179883 )

• mutants exhibit an increase in apoptotic cells in the lungs

respiratory system

increased lung apoptosis ( J:179883 )

• mutants exhibit an increase in apoptotic cells in the lungs

lung inflammation ( J:179883 )

• mutants exhibit infiltration of atypical foamy alveolar macrophages

• mutants with prolonged exposure to cigarette smoke exhibit perivascular and peribronchiolar inflammation

abnormal pulmonary alveolar system morphology ( J:179883 )

• 3 month old mutants exhibit enlarged air spaces and infiltration of atypical foamy alveolar macrophages

• progressive destruction of alveolar tissue

emphysema ( J:179883 )

• mutants develop progressive emphysema

abnormal pulmonary alveolar parenchyma morphology ( J:179883 )

• localized destruction leading to large cavities in the parenchyma

immune system

abnormal cytokine level ( J:179883 )

• elevated levels of IL-12p40, IL-13, and CXCL1 cytokines in the BAL

abnormal tumor necrosis factor level ( J:179883 )

• an elevated level of TNF-alpha is seen in the BAL fluid

lung inflammation ( J:179883 )

• mutants exhibit infiltration of atypical foamy alveolar macrophages

• mutants with prolonged exposure to cigarette smoke exhibit perivascular and peribronchiolar inflammation

homeostasis/metabolism

abnormal cytokine level ( J:179883 )

• elevated levels of IL-12p40, IL-13, and CXCL1 cytokines in the BAL

abnormal tumor necrosis factor level ( J:179883 )

• an elevated level of TNF-alpha is seen in the BAL fluid

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pulmonary emphysema		DOID:9675	OMIM:130700	J:179883

Genotype
MGI:5294554

cn10

• Allelic Composition: Jun^tm4Wag/Jun^tm4Wag; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

nervous system

nervous system phenotype ( J:176956 )

N • cultured neurons exhibit normal degeneration induced by NGF withdrawal

decreased neuron apoptosis ( J:176956 )

• in culture following NGF withdrawal

cellular

decreased neuron apoptosis ( J:176956 )

• in culture following NGF withdrawal

Genotype
MGI:4867644

cn11

• Allelic Composition: Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe; Jun^tm4Wag/Jun⁺; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

nervous system

abnormal neuron apoptosis ( J:166928 )

• neurosphere apoptosis is decreased compared to in Fbxw7^tm1Axbe/Fbxw7^tm1Axbe Tg(Nes-cre)1Kln mice

abnormal tectum morphology ( J:166928 )

• the cellularity defect in the mantle layer of the midbrain tectum observed in Fbxw7^tm1Axbe/Fbxw7^tm1Axbe Tg(Nes-cre)1Kln mice is rescued

• the number of stem cells in the tectal ventricular zone is increased compared to in wild-type mice

cellular

abnormal neuron apoptosis ( J:166928 )

• neurosphere apoptosis is decreased compared to in Fbxw7^tm1Axbe/Fbxw7^tm1Axbe Tg(Nes-cre)1Kln mice

Genotype
MGI:5578332

cn12

• Allelic Composition: Jun^tm4Wag/Jun^tm4Wag; Junb^tm3Wag/Junb^tm3Wag; Tg(Krt1-5-cre/ERT)1Ipc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

integument

skin inflammation ( J:116380 )

• intra-epidermal T cells, epidermal micro-abscesses and typical inflammatory-cell infiltrate consisting of neutrophils, and an increase in numbers of macrophages in the dermis are seen in mice 8-10 days after tamoxifen induction

abnormal skin morphology ( J:116380 )

• mice treated with tamoxifen show an increase in subepidermal vascularization

hyperkeratosis ( J:116380 )

• thickening of keratinized upper layers in mice treated with tamoxifen

parakeratosis ( J:116380 )

• in mice treated with tamoxifen

thick epidermis ( J:116380 )

• mice treated with tamoxifen show thickened epidermis with prominent rete ridge

psoriasis ( J:116380 )

• mice treated with tamoxifen at 8 weeks of age develop psoriasis-like skin lesions on hairless skin 8-10 days after tamoxifen induction, showing scaly plaques affecting primarily ears, paws and tail, and less frequently the hairy back skin

immune system

increased inflammatory response ( J:116380 )

• periostitis in mice treated with tamoxifen

autoimmune arthritis ( J:116380 )

• arthritic lesions similar to psoriatic arthritis are seen in 100% of mice treated with tamoxifen, showing inflammatory infiltrates in joint regions

skin inflammation ( J:116380 )

• intra-epidermal T cells, epidermal micro-abscesses and typical inflammatory-cell infiltrate consisting of neutrophils, and an increase in numbers of macrophages in the dermis are seen in mice 8-10 days after tamoxifen induction

skeleton

autoimmune arthritis ( J:116380 )

• arthritic lesions similar to psoriatic arthritis are seen in 100% of mice treated with tamoxifen, showing inflammatory infiltrates in joint regions

abnormal bone structure ( J:116380 )

• massive bone destruction

abnormal periosteum morphology ( J:116380 )

• periostitis in mice treated with tamoxifen

cardiovascular system

abnormal blood vessel morphology ( J:116380 )

• mice treated with tamoxifen show an increase in subepidermal vascularization

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
psoriasis		DOID:8893	OMIM:PS177900	J:116380

Genotype
MGI:7562246

cn13

• Allelic Composition: Jun^tm4Wag/Jun^tm4Wag; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

mortality/aging

mortality/aging ( J:199412 )

N • mice are present at the expected Mendelian ratios at E15.5-P0, indicating normal embryonic survival until late gestation or even until birth

cardiovascular system

cardiovascular system phenotype ( J:199412 )

N • at E15.5-P0, none of 10 mice examined exhibit any aortic arch artery remodeling defects

thin right ventricle myocardium compact layer ( J:199412 )

• at E15.5, three of 7 (43%) embryos show thinning of the compact myocardium of the right ventricle

• however, no compact zone thinning is noted in the left ventricle

double outlet right ventricle ( J:199412 )

• at E15.5-P0, one of 7 (14%) embryos exhibits a double outlet right ventricle (DORV)

thick mitral valve cusps ( J:199412 )

• at E15.5, mitral valve leaflets are thickened and hyperplastic in one embryo

mitral valve hyperplasia ( J:199412 )

• at E15.5-P0, one of 7 (14%) embryos shows mitral valve hyperplasia

perimembraneous ventricular septal defect ( J:199412 )

• at E15.5-P0, three of 7 (43%) embryos show a perimembranous VSD

thick pulmonary valve cusps ( J:199412 )

• at P0, pulmonary valve leaflets are thickened and hyperplastic in one embryo

pulmonary valve hyperplasia ( J:199412 )

• at E15.5-P0, one of 7 (14%) embryos shows pulmonary valve hyperplasia

muscle

thin right ventricle myocardium compact layer ( J:199412 )

• at E15.5, three of 7 (43%) embryos show thinning of the compact myocardium of the right ventricle

• however, no compact zone thinning is noted in the left ventricle

Genotype
MGI:2451292

cn14

• Allelic Composition: Jun^tm4Wag/Jun^tm4Wag; Tg(Alb1-cre)7Gsc/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

growth/size/body

decreased body size ( J:75863 )

• animals displayed reduced body weight at 2 weeks of age that persisted into adulthood

liver/biliary system

decreased liver weight ( J:75863 )

• reduced liver weight

abnormal liver regeneration ( J:75863 )

• following 70% partial hepatectomy, large areas of necrotic tissues were observed in the regenerating liver

Genotype
MGI:7562245

cn15

• Allelic Composition: Isl1^tm1(cre)Sev/Isl1⁺; Jun^tm4Wag/Jun⁺
• Genetic Background: Not Specified

cardiovascular system

interrupted aortic arch, type b ( J:199412 )

• at E14.5 to P0, a single embryo (1 of 22) shows IAA type B

• however, no other OFT or aortic arch abnormalities are observed