Phenotypes Associated with This Genotype

Genotype
MGI:3768245

• Allelic Composition: Nfkb1^tm1Bal/Nfkb1^tm1Bal
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

cellular

decreased B cell proliferation ( J:30268 , J:37184 )

• B cell proliferation following LPS and sCD40L stimulation is impaired (J:30268)

• however, B cells proliferate normally in response to CD40L, alpha-delta-dex and IL-4 + IL-5 (J:30268)

• B cells do not proliferate in response to LPS concentration that stimulate wild-type B cells to proliferate (J:37184)

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:37184 )

• mice die 24 hours after infection with Staphylococcus pneumoniae compared to wild-type mice that die between 36 and 72 hours after infection

decreased susceptibility to Picornaviridae infection induced morbidity/mortality ( J:37184 )

• mice are more resistant to EMC virus infection than wild-type mice and exhibit mortality at a 10-fold higher titer with a slower progression towards fatal encephalopathy

premature death ( J:37184 )

• mice die more frequently at a young age compared to wild-type mice

immune system

decreased B cell proliferation ( J:30268 , J:37184 )

• B cell proliferation following LPS and sCD40L stimulation is impaired (J:30268)

• however, B cells proliferate normally in response to CD40L, alpha-delta-dex and IL-4 + IL-5 (J:30268)

• B cells do not proliferate in response to LPS concentration that stimulate wild-type B cells to proliferate (J:37184)

large intestinal inflammation ( J:67107 )

• mice exhibit mild typhlocolitis

cecum inflammation ( J:67107 )

• mice exhibit mild typhlocolitis

peritoneal inflammation ( J:67107 )

• mild

abnormal class switch recombination ( J:30268 )

• B cells are defective in IgG3, IgE and IgA class switching but undergo substantial IgG1 class switching

decreased myeloid dendritic cell number ( J:77049 )

• low number of myeloid dendritic cells in Peyer's patches

abnormal Peyer's patch follicle morphology ( J:77049 )

• size of interfollicluar region is reduced

• slight increase of M cells in the follicle-associated epithelium (FAE)

abnormal Peyer's patch T cell area morphology ( J:77049 )

• CD3+ T cell numbers are reduced and T-cell areas of Peyer's patches are underrepresented and small in size

abnormal Peyer's patch germinal center morphology ( J:77049 )

• germinal centers are reduced in number and size with a low number of myeloid dentritic cells

decreased Peyer's patch number ( J:77049 )

• average of 2 to 4 Peyer's patches per mouse compared to an observed average of 7 to 10 per control mouse

small Peyer's patches ( J:77049 )

• Peyer's patches are smaller and contain a range of no more than 1 to 2 follicles

abnormal humoral immune response ( J:37184 )

• total NP-binding following exposure to NP15-CG is lower than in wild-type mice and NP-specific antibodies of all isotypes are decreased compared to in wild-type mice

decreased immunoglobulin level ( J:37184 )

• immunoglobin levels are 4-fold lower than in wild-type mice

• all isotypes except IgM are reduced

decreased IgA level ( J:37184 )

• IgA levels are decreased 5-fold

decreased IgE level ( J:37184 )

• IgE levels are decreased 50-fold

decreased IgG1 level ( J:37184 )

• IgG1 levels are reduced 10-fold

decreased IgM level ( J:30268 )

• proliferating B cells stimulated with alpha-delta-dex and IL-4 + IL-5 produce 32-fold less IgM than wild-type

• proliferating B cells stimulated wth mCD40L + IL-4 + IL-5 produce 41-fold less IgM than wild-type

• however, mlg and CD40 signaling restores B cell maturation to IgM secretion

decreased interleukin-6 secretion ( J:37184 )

• LPS-stimulated macrophages release 6-fold less IL-6

increased susceptibility to bacterial infection ( J:37184 , J:67107 )

• mice are more prone to infection than wild-type mice (J:37184)

• while mice efficiently clear extracellular bacteria they fail to clear intracellular bacteria (J:37184)

• 6 days after infection with Listeria monocytogenes, mice exhibit no peritoneal bacterial but several thousand splenic bacteria compared to wild-type mice that exhibit neither (J:37184)

• mice die 24 hours after infection with Staphylococcus pneumoniae compared to wild-type mice that die between 36 and 72 hours after infection (J:37184)

• however, mice do not exhibit any abnormal response to H. influenzae and E. coli infection (J:37184)

• mice are more sensitive to typhlocolitis induced by H. hepaticus than wild-type mice but less sensitive than Nfkb1^tm1Bal/Nfkb1^tm1Bal Rela^tm1Bal/Rela⁺ (J:67107)

increased susceptibility to bacterial infection induced morbidity/mortality ( J:37184 )

• mice die 24 hours after infection with Staphylococcus pneumoniae compared to wild-type mice that die between 36 and 72 hours after infection

decreased susceptibility to Picornaviridae infection induced morbidity/mortality ( J:37184 )

• mice are more resistant to EMC virus infection than wild-type mice and exhibit mortality at a 10-fold higher titer with a slower progression towards fatal encephalopathy

digestive/alimentary system

diarrhea ( J:67107 )

• mild

abnormal colon morphology ( J:67107 )

• mice exhibit mild colonic perforations and typhlocolitis

large intestinal inflammation ( J:67107 )

• mice exhibit mild typhlocolitis

cecum inflammation ( J:67107 )

• mice exhibit mild typhlocolitis

peritoneal inflammation ( J:67107 )

• mild

hematopoietic system

decreased B cell proliferation ( J:30268 , J:37184 )

• B cell proliferation following LPS and sCD40L stimulation is impaired (J:30268)

• however, B cells proliferate normally in response to CD40L, alpha-delta-dex and IL-4 + IL-5 (J:30268)

• B cells do not proliferate in response to LPS concentration that stimulate wild-type B cells to proliferate (J:37184)

abnormal class switch recombination ( J:30268 )

• B cells are defective in IgG3, IgE and IgA class switching but undergo substantial IgG1 class switching

decreased myeloid dendritic cell number ( J:77049 )

• low number of myeloid dendritic cells in Peyer's patches

decreased immunoglobulin level ( J:37184 )

• immunoglobin levels are 4-fold lower than in wild-type mice

• all isotypes except IgM are reduced

decreased IgA level ( J:37184 )

• IgA levels are decreased 5-fold

decreased IgE level ( J:37184 )

• IgE levels are decreased 50-fold

decreased IgG1 level ( J:37184 )

• IgG1 levels are reduced 10-fold

decreased IgM level ( J:30268 )

• proliferating B cells stimulated with alpha-delta-dex and IL-4 + IL-5 produce 32-fold less IgM than wild-type

• proliferating B cells stimulated wth mCD40L + IL-4 + IL-5 produce 41-fold less IgM than wild-type

• however, mlg and CD40 signaling restores B cell maturation to IgM secretion