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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Ikbkbtm1Ver
targeted mutation 1, Inder M Verma
MGI:2386269
Summary 4 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Ikbkbtm1Ver/Ikbkbtm1Ver involves: 129S4/SvJae * C57BL/6J MGI:3609489
cx2
Chuktm1Ver/Chuktm1Ver
Ikbkbtm1Ver/Ikbkbtm1Ver
Tnfrsf1atm1Mak/Tnfrsf1atm1Mak
involves: 129/Sv * 129S4/SvJae * C57BL/6J MGI:3609629
cx3
Ikbkbtm1Ver/Ikbkbtm1Ver
Tnfrsf1atm1Mak/Tnfrsf1atm1Mak
involves: 129S2/SvPas * 129S4/SvJae * C57BL/6J MGI:3609627
cx4
Chuktm1Ver/Chuktm1Ver
Ikbkbtm1Ver/Ikbkbtm1Ver
involves: 129S4/SvJae * C57BL/6J MGI:3609628


Genotype
MGI:3609489
hm1
Allelic
Composition
Ikbkbtm1Ver/Ikbkbtm1Ver
Genetic
Background
involves: 129S4/SvJae * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ikbkbtm1Ver mutation (0 available); any Ikbkb mutation (56 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• prior to E12.5, homozygotes appear morphologically normal; however, mutant embryos die progressively from E12.5 to E14 as a result of massive liver degeneration

liver/biliary system
• dead or moribund mutant embryos exhibit massive liver hemorrhage
• at E13, homozygotes exhibit extensive hepatocyte apoptosis, as shown by TUNEL assays
• at E13, mutant hepatocytes appear dissociated and dying, as evidenced by the presence of pyknotic nuclei; however, fetal liver hematopoeisis appears unaffected
• at E13 and E13.5, surviving homozygotes are of normal body size and morphology but exhibit smaller and darker livers than wild-type mice
• dead or moribund mutant embryos exhibit massive liver degeneration

cardiovascular system
• dead or moribund mutant embryos exhibit massive liver hemorrhage

cellular
• mutant MEFs exhibit significantly reduced NF-kappaB activation upon induction with TNF or IL-1alpha
• mutant MEFs exhibit increased sensitivity to TNF-induced apoptosis relative to wild-type or heterozygous MEFs
• at E13, homozygotes exhibit extensive hepatocyte apoptosis, as shown by TUNEL assays




Genotype
MGI:3609629
cx2
Allelic
Composition
Chuktm1Ver/Chuktm1Ver
Ikbkbtm1Ver/Ikbkbtm1Ver
Tnfrsf1atm1Mak/Tnfrsf1atm1Mak
Genetic
Background
involves: 129/Sv * 129S4/SvJae * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chuktm1Ver mutation (0 available); any Chuk mutation (51 available)
Ikbkbtm1Ver mutation (0 available); any Ikbkb mutation (56 available)
Tnfrsf1atm1Mak mutation (2 available); any Tnfrsf1a mutation (52 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• triple homozygotes survive to ~E16.5, exhibiting a morphology similar to that observed in Chuktm1Ver mutant embryos

limbs/digits/tail
• at E14.5, triple homozygotes exhibit dumpy limb buds, similar to those observed in Chuktm1Ver mutant embryos
• at E14.5, triple homozygotes exhibit curled tails, similar to those observed in Chuktm1Ver mutant embryos

nervous system
• at E14.5, triple homozygotes exhibit a neural tube defect, similar to that observed in mice doubly homozygous for Chuktm1Ver and Ikbkbtm1Ver

embryo
• at E14.5, triple homozygotes exhibit dumpy limb buds, similar to those observed in Chuktm1Ver mutant embryos
• at E14.5, triple homozygotes exhibit a neural tube defect, similar to that observed in mice doubly homozygous for Chuktm1Ver and Ikbkbtm1Ver




Genotype
MGI:3609627
cx3
Allelic
Composition
Ikbkbtm1Ver/Ikbkbtm1Ver
Tnfrsf1atm1Mak/Tnfrsf1atm1Mak
Genetic
Background
involves: 129S2/SvPas * 129S4/SvJae * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ikbkbtm1Ver mutation (0 available); any Ikbkb mutation (56 available)
Tnfrsf1atm1Mak mutation (2 available); any Tnfrsf1a mutation (52 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• double homozygotes develop to term but die within the first postnatal month, unlike Ikbkbtm1Ver mutant embryos that die at ~E12.5-E13.5




Genotype
MGI:3609628
cx4
Allelic
Composition
Chuktm1Ver/Chuktm1Ver
Ikbkbtm1Ver/Ikbkbtm1Ver
Genetic
Background
involves: 129S4/SvJae * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chuktm1Ver mutation (0 available); any Chuk mutation (51 available)
Ikbkbtm1Ver mutation (0 available); any Ikbkb mutation (56 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• double mutant embryos are obtained at the expected frequency at E11.5, but die at E12 as a result of liver dysfunction

liver/biliary system
• at E11.5-E12, double homozygotes exhibit a massive increase in liver apoptosis relative to wild-type embryos, indicating liver dysfunction

nervous system
• at E9.5, increased apoptosis is noted in the neuroepithelium of double mutant hindbrain
• at E9.5, double homozygous mutant embryos show increased apoptosis in the neuronal epithelium at the hindbrain level
• however, no defects in neural differentiation are observed
• at ~E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in the spinal cord relative to wild-type mice
• ~70% of double homozygotes fail to close the neural tube in the hindbrain
• double mutant embryos exhibit reduced telencephalic vesicles relative to wild-type embryos
• at E9.5, double homozygotes lack the roof of hindbrain
• at about E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in dorsal root ganglia relative to wild-type mice

cellular
• double mutant MEFs exhibit no detectable NF-kappaB DNA binding activity upon induction with human TNF, IL-1alpha, or LPS
• notably, NF-kappaB activation is more attenuated in single Ikbkbtm1Ver mutant MEFs than in single Chuktm1Ver mutant MEFs
• at E9.5, increased apoptosis is noted in the neuroepithelium of double mutant hindbrain
• at E11.5-E12, double homozygotes exhibit a massive increase in liver apoptosis relative to wild-type embryos, indicating liver dysfunction
• at E9.5, double homozygous mutant embryos show increased apoptosis in the neuronal epithelium at the hindbrain level
• however, no defects in neural differentiation are observed
• at ~E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in the spinal cord relative to wild-type mice

embryo
• at E9.5, double homozygotes exhibit defective neurulation: neural folds at the hindbrain level fail to elevate on either side of the midline and do not bend toward each other
• ~70% of double homozygotes fail to close the neural tube in the hindbrain





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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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last database update
11/12/2024
MGI 6.24
The Jackson Laboratory