Phenotypes associated with this allele
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ikbkbtm1Ver mutation
(0 available);
any
Ikbkb mutation
(54 available)
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mortality/aging
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• 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
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liver/biliary system
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• dead or moribund mutant embryos exhibit massive liver hemorrhage
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• at E13, homozygotes exhibit extensive hepatocyte apoptosis, as shown by TUNEL assays
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• at E13, mutant hepatocytes appear dissociated and dying, as evidenced by the presence of pyknotic nuclei; however, fetal liver hematopoeisis appears unaffected
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• at E13 and E13.5, surviving homozygotes are of normal body size and morphology but exhibit smaller and darker livers than wild-type mice
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• dead or moribund mutant embryos exhibit massive liver degeneration
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cardiovascular system
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• dead or moribund mutant embryos exhibit massive liver hemorrhage
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cellular
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• mutant MEFs exhibit significantly reduced NF-kappaB activation upon induction with TNF or IL-1alpha
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• mutant MEFs exhibit increased sensitivity to TNF-induced apoptosis relative to wild-type or heterozygous MEFs
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• at E13, homozygotes exhibit extensive hepatocyte apoptosis, as shown by TUNEL assays
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chuktm1Ver mutation
(0 available);
any
Chuk mutation
(48 available)
Ikbkbtm1Ver mutation
(0 available);
any
Ikbkb mutation
(54 available)
Tnfrsf1atm1Mak mutation
(2 available);
any
Tnfrsf1a mutation
(47 available)
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mortality/aging
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• triple homozygotes survive to ~E16.5, exhibiting a morphology similar to that observed in Chuktm1Ver mutant embryos
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limbs/digits/tail
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• at E14.5, triple homozygotes exhibit dumpy limb buds, similar to those observed in Chuktm1Ver mutant embryos
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• at E14.5, triple homozygotes exhibit curled tails, similar to those observed in Chuktm1Ver mutant embryos
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nervous system
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• at E14.5, triple homozygotes exhibit a neural tube defect, similar to that observed in mice doubly homozygous for Chuktm1Ver and
Ikbkbtm1Ver
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embryo
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• at E14.5, triple homozygotes exhibit dumpy limb buds, similar to those observed in Chuktm1Ver mutant embryos
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• at E14.5, triple homozygotes exhibit a neural tube defect, similar to that observed in mice doubly homozygous for Chuktm1Ver and
Ikbkbtm1Ver
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ikbkbtm1Ver mutation
(0 available);
any
Ikbkb mutation
(54 available)
Tnfrsf1atm1Mak mutation
(2 available);
any
Tnfrsf1a mutation
(47 available)
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mortality/aging
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• double homozygotes develop to term but die within the first postnatal month, unlike Ikbkbtm1Ver mutant embryos that die at ~E12.5-E13.5
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chuktm1Ver mutation
(0 available);
any
Chuk mutation
(48 available)
Ikbkbtm1Ver mutation
(0 available);
any
Ikbkb mutation
(54 available)
|
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mortality/aging
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• double mutant embryos are obtained at the expected frequency at E11.5, but die at E12 as a result of liver dysfunction
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liver/biliary system
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• at E11.5-E12, double homozygotes exhibit a massive increase in liver apoptosis relative to wild-type embryos, indicating liver dysfunction
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nervous system
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• at E9.5, increased apoptosis is noted in the neuroepithelium of double mutant hindbrain
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• 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
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• at ~E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in the spinal cord relative to wild-type mice
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• ~70% of double homozygotes fail to close the neural tube in the hindbrain
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• double mutant embryos exhibit reduced telencephalic vesicles relative to wild-type embryos
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• at E9.5, double homozygotes lack the roof of hindbrain
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• at about E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in dorsal root ganglia relative to wild-type mice
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cellular
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• 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
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• at E9.5, increased apoptosis is noted in the neuroepithelium of double mutant hindbrain
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• at E11.5-E12, double homozygotes exhibit a massive increase in liver apoptosis relative to wild-type embryos, indicating liver dysfunction
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• 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
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• at ~E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in the spinal cord relative to wild-type mice
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embryo
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• 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
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• ~70% of double homozygotes fail to close the neural tube in the hindbrain
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