Phenotypes Associated with This Genotype

Genotype
MGI:3609628

• Allelic Composition: Chuk^tm1Ver/Chuk^tm1Ver; Ikbkb^tm1Ver/Ikbkb^tm1Ver
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:63443 )

• 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

increased hepatocyte apoptosis ( J:63443 )

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

liver degeneration ( J:63443 )

nervous system

increased hindbrain apoptosis ( J:63443 )

• at E9.5, increased apoptosis is noted in the neuroepithelium of double mutant hindbrain

increased embryonic neuroepithelium apoptosis ( J:63443 )

• 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

increased spinal cord apoptosis ( J:63443 )

• at ~E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in the spinal cord relative to wild-type mice

open neural tube ( J:63443 )

• ~70% of double homozygotes fail to close the neural tube in the hindbrain

small embryonic telencephalon ( J:63443 )

• double mutant embryos exhibit reduced telencephalic vesicles relative to wild-type embryos

abnormal hindbrain morphology ( J:63443 )

• at E9.5, double homozygotes lack the roof of hindbrain

abnormal dorsal root ganglion morphology ( J:63443 )

• at about E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in dorsal root ganglia relative to wild-type mice

cellular

abnormal cell physiology ( J:63443 )

• 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 Ikbkb^tm1Ver mutant MEFs than in single Chuk^tm1Ver mutant MEFs

increased hindbrain apoptosis ( J:63443 )

• at E9.5, increased apoptosis is noted in the neuroepithelium of double mutant hindbrain

increased hepatocyte apoptosis ( J:63443 )

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

increased embryonic neuroepithelium apoptosis ( J:63443 )

• 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

increased spinal cord apoptosis ( J:63443 )

• at ~E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in the spinal cord relative to wild-type mice

embryo

abnormal neural fold elevation formation ( J:63443 )

• 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

open neural tube ( J:63443 )

• ~70% of double homozygotes fail to close the neural tube in the hindbrain