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Strain Name:

B6;129P-Nfkb1tm1Bal/J

Stock Number:

002849

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General Terms and Conditions

Former Name      B6;129P2-Nfkb1tm1Bal/J    (Changed: 13-MAR-06 )
Genes & Alleles   Nfkb1;   Nfkb1tm1Bal;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Strain
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Targeted Mutation
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator David Baltimore,   California Institute of Technology
GenerationF?+31 (20-DEC-06)

Appearance
pink-eyed light-bellied agouti, yellow coat
Related Genotype: Aw/Aw Oca2p/Oca2p

Strain Description
Mice homozygous for the Nfkb1tm1Bal targeted mutation are viable and fertile. Homozygous mutant mice exhibit defective B cell responses, defective responses to infection, and also defects in basal and specific antibody production.

Strain Development
Exon 6 of the Nfkb1 gene was disrupted by insertion of a vector containing the neo resistance gene. The 129-derived E14 ES cell line was used.

Mammalian Phenotype Terms assigned by genotype

Nfkb1tm1Bal/Nfkb1tm1Bal

        B6;129P-Nfkb1tm1Bal/J
  • hearing/vestibular/ear phenotype
  • abnormal cochlear inner hair cell morphology (MGI Ref ID J:107245)
    • at 1 and 3 months, vacuole-like spaces replace the afferent terminals of the inner radial nerves while efferent inner spiral fibers appear intact
    • at 1 and 3 months, edematous-appearing extracellular spaces are noted between the IHC and supporting cells; the cytoplasm in the base of IHCs consists of numerous small vesicles infiltrated with mitochondria and short profiles of cisternae
    • in contrast, no major pathological changes are seen in mutant OHCs or stria vascularis at 1 or 3 months
    • all homozygotes (6 of 6) exhibit excitotoxic pathologies of afferent dendrites under the IHCs compared with 4 of 9 in wild type mice
    • homozygotes show a significantly higher number of swollen dendritic terminals per IHC region relative to wild type mice; only type I ganglion neurons are involved
  • decreased cochlear nerve compound action potential (MGI Ref ID J:107245)
    • at 1 month of age, CAP thresholds in homozygotes are elevated by 6-20 dB SPL relative to wild-type mice at almost all frequencies
    • at 3 months of age, mutant CAP thresholds are increased by ~20 dB SPL at low frequencies and by ~30 dB at high frequencies relative to wild type
    • by 8 months of age, most homozygotes no longer respond to auditory stimuli at high frequencies (90 dB SPL), whereas wild type mice retain CAP responses at most test frequencies
    • at 3 months, no sigificant loss of distorion product otoacoustic emissions (DPOAEs) is noted when primaries are presented at 70 dB SPL
    • no significant differences in mean endocochlear potential values are observed at 1, 3, and 8 months of age relative to wild type mice
  • increased susceptibility to age-related hearing loss (MGI Ref ID J:107245)
    • homozygotes exhibit accelerated age-related hearing loss at higher frequencies, as assessed by CAP threshold shifts at 1, 3, and 8 months of age
    • accelerated hearing loss is highly associated with an exacerbated excitotoxic-like damage in afferent dendrites under IHCs and an accelerated loss of spiral ganglion neurons
  • increased susceptibility to noise-induced hearing loss (MGI Ref ID J:107245)
    • at 2 hrs after exposure to a wideband, low-level noise at 70 dB SPL, 1-month-old homozygotes display 7-15 dB SPL threshold shifts across most test frequencies whereas wild type mice show no significant CAP threshold shifts
  • nervous system phenotype
  • abnormal cochlear inner hair cell morphology (MGI Ref ID J:107245)
    • at 1 and 3 months, vacuole-like spaces replace the afferent terminals of the inner radial nerves while efferent inner spiral fibers appear intact
    • at 1 and 3 months, edematous-appearing extracellular spaces are noted between the IHC and supporting cells; the cytoplasm in the base of IHCs consists of numerous small vesicles infiltrated with mitochondria and short profiles of cisternae
    • in contrast, no major pathological changes are seen in mutant OHCs or stria vascularis at 1 or 3 months
    • all homozygotes (6 of 6) exhibit excitotoxic pathologies of afferent dendrites under the IHCs compared with 4 of 9 in wild type mice
    • homozygotes show a significantly higher number of swollen dendritic terminals per IHC region relative to wild type mice; only type I ganglion neurons are involved
  • cochlear ganglion degeneration (MGI Ref ID J:107245)
    • at 8 months, homozygotes show a 69% loss of SGNs in the basal cochlea relative to a ~28% loss observed in wild type mice
    • at 8 months, the numbers of afferent axons per habenular opening are significantly reduced relative to those of wild type mice
    • however, no significant differences in IHC or OHC loss are noted at 8 months relative to wild type mice
  • decreased cochlear nerve compound action potential (MGI Ref ID J:107245)
    • at 1 month of age, CAP thresholds in homozygotes are elevated by 6-20 dB SPL relative to wild-type mice at almost all frequencies
    • at 3 months of age, mutant CAP thresholds are increased by ~20 dB SPL at low frequencies and by ~30 dB at high frequencies relative to wild type
    • by 8 months of age, most homozygotes no longer respond to auditory stimuli at high frequencies (90 dB SPL), whereas wild type mice retain CAP responses at most test frequencies
    • at 3 months, no sigificant loss of distorion product otoacoustic emissions (DPOAEs) is noted when primaries are presented at 70 dB SPL
    • no significant differences in mean endocochlear potential values are observed at 1, 3, and 8 months of age relative to wild type mice
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype (MGI Ref ID J:91366)
    • despite altered expression of Trp53, neurons exhibit normal camptothecin-induced neuronal death
    • abnormal calcium ion homeostasis (MGI Ref ID J:107245)
      • at 8 months, the immunoreactivity for a set of calcium-buffering proteins is significantly increased in mutant spiral ganglion neurons, suggesting impaired calcium ion homeostasis
  • immune system phenotype
  • *normal* immune system phenotype (MGI Ref ID J:118907)
    • most pancreatic islet cells appear normal in mutants not developing diabetes after streptozotocin treatment, while control pancreatic islets display insulitis; mutants developing diabetes after treatment display insulis in many islets
    • abnormal CD4-positive T cell physiology (MGI Ref ID J:118907)
      • splenocytes treated with anti-CD3 with or without anti-CD28 antibodies produce reduced levels of interferon gamma and Il-2 (Th1 cytokines) but increased levels of Il-4 and Il-10 (Th2 cytokines) while wild-type splenocytes produce both Th1 and Th2 cytokines
    • abnormal antigen presenting cell physiology (MGI Ref ID J:118907)
      • abnormal dendritic cell physiology (MGI Ref ID J:118907)
        • bone marrow-derived dendritic cells stimulated with LPS produce significantly less Il-12p40 and TNF alpha than stimulated wild-type dendritic cells
      • abnormal macrophage physiology (MGI Ref ID J:118907)
        • peritoneal macrophages produce less Il-6, Il-12p40, TNF alpha, and nitric oxide compared to wild-type cells upon stimulation with interferon gamma and/or LPS
    • abnormal cytokine secretion (MGI Ref ID J:79107)
      • Il-4 secretion is impaired in cultured cells upon stimulation with MOG peptide
    • decreased susceptibility to autoimmune diabetes (MGI Ref ID J:118907)
      • >70% of control mice treated with low dose streptozotocin for 5 days develop diabetes starting ~8 and 12 days after the first injection, but only 23% of mutants develop diabetes
  • cellular phenotype
  • increased apoptosis (MGI Ref ID J:118907)
    • growth factor withdrawal from cultured bone marrow dendritic cells enhances apoptosis of dendritic cells, but not granulocytes or macrophages
  • muscle phenotype
  • *normal* muscle phenotype (MGI Ref ID J:135692)
    • myogenesis is normal

Nfkb1tm1Bal/Nfkb1tm1Bal

        involves: 129P2/OlaHsd * C57BL/6
  • life span-post-weaning/aging
  • abnormal induced morbidity/mortality (MGI Ref ID 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
  • premature death (MGI Ref ID J:37184)
    • mice die more frequently at a young age compared to wild type mice
  • immune system phenotype
  • abnormal class switch recombination (MGI Ref ID J:30268)
    • B cells are defective in IgG3, IgE and IgA class switching but undergo substantial IgG1 class switching
  • abnormal humoral immune response (MGI Ref ID 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 (MGI Ref ID J:37184)
      • immunoglobin levels are 4-fold lower than in wild type mice
      • all isotypes except IgM are reduced
      • decreased IgA level (MGI Ref ID J:37184)
        • IgA levels are decreased 5-fold
      • decreased IgE level (MGI Ref ID J:37184)
        • IgE levels are decreased 50-fold
      • decreased IgG1 level (MGI Ref ID J:37184)
        • IgG1 levels are reduced 10-fold
      • decreased IgM level (MGI Ref ID 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 B cell proliferation (MGI Ref ID J:37184)
    • B cells do not proliferate in response to LPS concentration that stimulate wild type B cells to proliferate
    • B cell proliferation following LPS and sCD40L stimulation is impaired
    • however, B cells proliferate normally in response to CD40L, alpha-delta-dex and IL-4 + IL-5
  • decreased interleukin-6 secretion (MGI Ref ID J:37184)
    • LPS-stimulated macrophages release 6-fold less IL-6
  • decreased susceptibility to viral infection (MGI Ref ID 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
  • increased susceptibility to infection (MGI Ref ID J:37184)
    • mice are more prone to infection than wild type mice
    • while mice efficiently clear extracellular bacteria they fail to clear intracellular bacteria
    • 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
    • mice die 24 hours after infection with Staphylococcus pneumoniae compared to wild type mice that die between 36 and 72 hours after infection
    • however, mice do not exhibit any abnormal response to H. influenzae and E. coli infection
    • increased susceptibility to bacterial infection (MGI Ref ID J:67107)
      • mice are more sensitive to typhlocolitis induced by H. hepaticus than wild type mice but less sensitive than Nfkb1tm1Bal/Nfkb1tm1Bal Relatm1Bal/Rela+
  • large intestinal inflammation (MGI Ref ID J:67107)
    • mice exhibit mild typhlocolitis
  • peritoneal inflammation (MGI Ref ID J:67107)
    • mild
  • digestive/alimentary phenotype
  • abnormal cecum morphology (MGI Ref ID J:67107)
    • mice exhibit mild typhlocolitis
  • abnormal colon morphology (MGI Ref ID J:67107)
    • mice exhibit mild colonic perforations and typhlocolitis
  • diarrhea (MGI Ref ID J:67107)
    • mild
  • large intestinal inflammation (MGI Ref ID J:67107)
    • mice exhibit mild typhlocolitis
  • peritoneal inflammation (MGI Ref ID J:67107)
    • mild
  • hematopoietic system phenotype
  • abnormal class switch recombination (MGI Ref ID J:30268)
    • B cells are defective in IgG3, IgE and IgA class switching but undergo substantial IgG1 class switching
  • decreased B cell proliferation (MGI Ref ID J:37184)
    • B cells do not proliferate in response to LPS concentration that stimulate wild type B cells to proliferate
    • B cell proliferation following LPS and sCD40L stimulation is impaired
    • however, B cells proliferate normally in response to CD40L, alpha-delta-dex and IL-4 + IL-5

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Nfkb1tm1Bal/Nfkb1tm1Bal

        Background Not Specified
  • immune system phenotype
  • abnormal Peyer's patch morphology (MGI Ref ID J:77049)
    • increased CD3+ T cell count, resulting in decreased B220+ B cells/CD3+ T cell ratio
    • abnormal Peyer's patch follicle morphology (MGI Ref ID J:77049)
      • while follicles were clearly demarcated at E13.5, they were reduced in number and in size
    • decreased Peyer's patch number (MGI Ref ID J:77049)
      • average of 2 to 4 Peyer's patches per mouse compared to an observed average of 7 to 10 per control mouse

Nfkb1tm1Bal/Nfkb1tm1Bal

        involves: 129P2/OlaHsd
  • immune system phenotype
  • *normal* immune system phenotype (MGI Ref ID J:113514)
    • mice exhibit normal dendritic cell development and maturation
    • decreased marginal zone B cell number (MGI Ref ID J:65246)
  • hematopoietic system phenotype
  • decreased marginal zone B cell number (MGI Ref ID J:65246)

Gene & Allele Details

Allele Symbol Nfkb1tm1Bal
Allele Name targeted mutation 1, David Baltimore
Common Name(s) NF-kappaB1 KO; NF-kappaB1-; NF-kappaBtm1Bal; NFkappaB10; Nfkappab1-; Nfkb1-; p50-; p50KO;
Mutation Made By David Baltimore,   California Institute of Technology
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Nfkb1, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1, p105
Chromosome 3
Gene Common Name(s) DKFZp686C01211; EBP-1; KBF1; MGC54151; NF kappaB1; NF-kB; NF-kappa-B; NF-kappaB; NFKB-p105; NFKB-p50; nuclear factor kappaB p50; p105; p50; p50 subunit of NF kappaB; p50/p105;
General Note

Effect of reconstitution with Nfkb1tm1Bal homozygous hematopoietic cells on atherogenesis in atherosclerosis prone mice

To assess the role of NFKB1 in atherogenesis, mice homozygous for a mutation of the low density lipoprotein receptor (Ldlrtm1Her) were lethally irradiated and transplanted with bone marrow from Nfkb1tm1Bal homozygous mice and 4 weeks later placed on a high-fat diet for 10 weeks. Aortic root lesion area of mice with NFKB1-deficient hematopoietic cells was 41% smaller than in control mice. Whereas control lesions contained primarily large foam cells, lesions of mice reconstituted with NFKB1-deficient bone marrow contained large numbers of small, inflammatory cells and very few foam cells. 3-fold as many cells attached to the lesion cap in transplanted mice. Most cells in control lesions were macrophages, while in transplanted mice there was a preponderance of T and B lymphocytes.

Macrophages induced to differentiate in culture from NFKB1-deficient bone marrow exhibited differences versus control macrophages in the secretion patterns of several cytokines following lipopolysaccharide (LPS) stimulation. Whereas control macrophages expressed high levels of scavenger receptor class A (SR-A) in response to LPS, this response was greatly attenuated in mice with NFKB1-deficient hematopoietic systems; uptake of oxidized low density lipoprotein (oxLDL) was similarly diminished, although neither parameter differed between transplant and control macrophages in the absence of stimulation. J:87639

Molecular Note Insertion of a PGK-neomycin resistance cassette into exon 6 disrupted the gene. Exon 6 encodes the p105 precursor of the p50 subunit of the encoded transcription factor. The authors predict that this allele produces a truncated polypeptide that cannot bind with DNA, or dimerize with itself or other kappaB binding motifs. [MGI Ref ID J:37184]

Control Information

  Allele   Control
 Nfkb1tm1Bal  100903 B6129PF2/J (approximate)
 
  Considerations for Choosing Controls

Genotyping Protocols

Nfkb1tm1Bal

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying   Nfkb1tm1Bal allele
006097   B6.Cg-Nfkb1tm1Bal/J
View Strains carrying   Nfkb1tm1Bal     (1 strain)

Additional Web Information

Genetic Quality Control Annual Report
JAX® NOTES, Summer 2005; 498. Toll-like Receptor JAX? Mice for Immunological Research.

Animal Health Reports

Room Number           AX12

Research Applications

This mouse can be used to support research in many areas including:

Nfkb1tm1Bal related

Immunology and Inflammation Research
Immunodeficiency (Inflammatory bowel disease)

References

Selected Reference(s)

Sha WC; Liou HC; Tuomanen EI; Baltimore D. 1995. Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses. Cell 80(2):321-30. [PubMed: 7834752]  [MGI Ref ID J:37184]

Additional References

Price and Supply Information

Strain Name: B6;129P-Nfkb1tm1Bal/J
Stock Number: 002849

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.
LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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