Phenotypes associated with this allele

• Allele Symbol: Jun^tm1Wag
• Allele Name: targeted mutation 1, Erwin F Wagner
• Allele ID: MGI:2149630
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Jun^tm1Wag/Jun^tm1Wag	either: (involves: 129S2/SvPas) or (involves: 129S2/SvPas * C57BL/6)	MGI:3622270
hm2	Jun^tm1Wag/Jun^tm1Wag	involves: 129S2/SvPas	MGI:2179847
hm3	Jun^tm1Wag/Jun^tm1Wag	involves: 129S2/SvPas * C57BL/6	MGI:2676189
ht4	Jun^tm1Wag/Jun^tm5.1(Junb)Wag	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6	MGI:3849575
cx5	Jun^tm1Wag/Jun^tm1Wag Tg(Junb)1598Angl/0	involves: 129S2/SvPas * C57BL/6	MGI:2662363

Genotype
MGI:3622270

hm1

• Allelic Composition: Jun^tm1Wag/Jun^tm1Wag
• Genetic Background: either: (involves: 129S2/SvPas) or (involves: 129S2/SvPas * C57BL/6)

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:14538 )

• homozygotes die between E11.5 and E15.5; no live homozygotes are recovered after E16.5

embryonic lethality during organogenesis, incomplete penetrance ( J:14538 )

• homozygotes die between E11.5 and E15.5, with frequent deaths noted at E13.5

liver/biliary system

increased hepatocyte apoptosis ( J:14538 )

• at E12.5, homozygotes often display hepatocyte apoptosis

abnormal bile duct development ( J:14538 )

• at E12.5, homozygotes display absence of developing ducts

abnormal liver development ( J:14538 )

• homozygotes exhibit defective fetal hepatogenesis

dissociated hepatocytes ( J:14538 )

• at E12.5, mutant livers display a hypoplastic epithelium with rounded, dissociated residual hepatocytes

hepatic necrosis ( J:14538 )

• at E12.5, homozygotes often display hepatocyte necrosis

homeostasis/metabolism

edema ( J:14538 )

• 5 of 8 E12.5 homozygotes and 2 of 2 E13.5-E14.5 homozygotes exhibit generalized edema

hematopoietic system

increased nucleated erythrocyte cell number ( J:14538 )

• homozygotes show enhanced fetal liver erythropoiesis with elevated numbers of nucleated erythroid cells, resulting in an erythroblastosis-like phenotype

nervous system

abnormal forebrain morphology ( J:14538 )

• at E12.5, homozygotes exhibit severe edema in the forebrain, as shown by large intercellular spaces

cardiovascular system

blood vessel congestion ( J:14538 )

• at E12.5, 1 of 8 homozygotes exhibited severely congested vessels and signs of early liver damage

endocrine/exocrine glands

abnormal bile duct development ( J:14538 )

• at E12.5, homozygotes display absence of developing ducts

cellular

increased hepatocyte apoptosis ( J:14538 )

• at E12.5, homozygotes often display hepatocyte apoptosis

Genotype
MGI:2179847

hm2

• Allelic Composition: Jun^tm1Wag/Jun^tm1Wag
• Genetic Background: involves: 129S2/SvPas

cellular

decreased cell proliferation ( J:175212 )

• in mouse embryonic fibroblasts

oxidative stress ( J:175212 )

• mouse embryonic fibroblasts and fetal liver cells produce more hydrogen peroxide than wild-type cells

Genotype
MGI:2676189

hm3

• Allelic Composition: Jun^tm1Wag/Jun^tm1Wag
• Genetic Background: involves: 129S2/SvPas * C57BL/6

Jun^tm1Wag/Jun^tm1Wag fetuses exhibit increased apoptosis in the liver

liver/biliary system

increased hepatocyte apoptosis ( J:55508 )

• at E13.0, 8 of 19 mutant fetal livers show significantly increased apoptosis of both hepatoblasts and erythroid cells; however, no deregulation of apoptosis is noted at E12.5

• mutant fetal liver cells are able to reconstitute all hematopoietic compartments of lethally irradiated recipient mice, indicating that hematopoietic cell apoptosis is likely not due to a cell-autonomous defect

• in vitro, primary hepatoblasts and fibroblasts obtained from E12.5 homozygotes show a ~4-fold increase in apoptosis relative to wild-type cells

decreased hepatocyte proliferation ( J:55508 )

• in vitro, primary hepatoblasts and fibroblasts obtained from E12.5 homozygotes display a ~50% reduction in mitotic capacity as shown by [³H]thymidine incorporation

cardiovascular system

right aortic arch ( J:55508 )

• at E12.5, some homozygotes display abnormal remodeling of the aortic arch arteries resulting in a right-sided aortic arch

persistent truncus arteriosus ( J:55508 )

• at E12.5, all (19 of 19) homozygotes exhibit a single outflow vessel arising from the right ventricle

ventricular septal defect ( J:55508 )

• at E14.5, homozygotes display incomplete septation of the left and right ventricles

decreased heart right ventricle wall thickness ( J:55508 )

• at E12.5, homozygotes display a thinner right ventricular wall

embryo

abnormal cardiac neural crest cell migration ( J:55508 )

• at E12.5, homozygotes exhibit reduced migration of neural crest cells in the outflow tract of the right ventricle

cellular

increased hepatocyte apoptosis ( J:55508 )

• at E13.0, 8 of 19 mutant fetal livers show significantly increased apoptosis of both hepatoblasts and erythroid cells; however, no deregulation of apoptosis is noted at E12.5

• mutant fetal liver cells are able to reconstitute all hematopoietic compartments of lethally irradiated recipient mice, indicating that hematopoietic cell apoptosis is likely not due to a cell-autonomous defect

• in vitro, primary hepatoblasts and fibroblasts obtained from E12.5 homozygotes show a ~4-fold increase in apoptosis relative to wild-type cells

abnormal cardiac neural crest cell migration ( J:55508 )

• at E12.5, homozygotes exhibit reduced migration of neural crest cells in the outflow tract of the right ventricle

decreased hepatocyte proliferation ( J:55508 )

• in vitro, primary hepatoblasts and fibroblasts obtained from E12.5 homozygotes display a ~50% reduction in mitotic capacity as shown by [³H]thymidine incorporation

Genotype
MGI:3849575

ht4

• Allelic Composition: Jun^tm1Wag/Jun^{tm5.1(Junb)Wag}
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:75359 )

• although mutant embryos are obtained at normal Mendelian ratios until E14.5, the frequency declines and no live mutant fetuses are recovered by E18.5

Genotype
MGI:2662363

cx5

• Allelic Composition: Jun^tm1Wag/Jun^tm1Wag; Tg(Junb)1598Angl/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:75359 )

• only a few mutant mice survive past weaning, with the oldest one reaching 7 months of age

perinatal lethality, incomplete penetrance ( J:75359 )

• although Mendelian ratios are recovered at E14.5-E18.5, only some viable mutant mice are born

postnatal lethality, incomplete penetrance ( J:75359 )

• only 4% of mutant mice reach weaning age

vision/eye

eyelids open at birth ( J:75359 )

• newborn mutant mice have open eyes but do not show any other overt defects

cardiovascular system

cardiovascular system phenotype ( J:75359 )

N • at E12.5, mutant fetuses exhibit normal formation of the aorta and pulmonary artery, indicating that development of the cardiac outflow tract is unaffected

liver/biliary system

liver/biliary system phenotype ( J:75359 )

N • at E15.5, mutant fetuses display normal liver architecture

cellular

abnormal cell proliferation ( J:75359 )

• similar to primary MEFs isolated from E12.5 Jun^tm1(Junb)Wag homozygotes, these mutant MEFs do not enter premature senescence and show increased proliferation relative to Jun^tm1Wag cells, but do not proliferate as fast as wild-type cells