Overview

NFKB2/p52 transgenic mice express an N terminal truncation of the NFKB2 protein in lymphocytes. Mice exhibit inflammation in the lungs, salivary glands and kidneys, and immune complex glomerulonephritis. These mice may be useful for studies involving NFKB2 signaling pathways and autoimmunity.

Donating Investigator

Han-Fei Ding, Georgia Health Sciences University

Genetic overview

Genetic Background	Generation

Tg(H2-K^b-NFKB2*)452Hfdg

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research

View All Research Applications

Details

Detailed Description

NFKB2/p52 transgenic mice express an N terminal truncation of the NFKB2 protein in lymphocytes. Approximately 76% of 6-12 month old hemizygous mice develop inflammation in the lungs, salivary glands and kidneys. Both spleen and lymph nodes sizes are increased. Inflammation is characterized by an infiltration of lymphocytes (in particular, activated B cells and CD4+ T cells) and macrophages. Serum from transgenic mice contains an 8.2 fold increase in anti-dsDNA autoantibodies as compared to wild-type. Approximately half of the mice develop immune complex glomerulonephritis. Autoimmune disease in these mice appears to be a function of p52 down-regulation of the pro-apoptotic protein BIM leading to defects in apoptosis of autoreactive lymphocytes. These mice may be useful for studies involving NFKB2 signaling pathways and autoimmunity.

Development

The transgenic construct contains the coding sequence for human NFKB2 p52 under the direction of an H2-K^b promoter and an immunoglobulin mu chain enhancer. The p52 truncation mutant codes for the N-terminal 442 amino acids of NFKB2. The construct was microinjected into (C57BL/6J and SJL/J)F2 fertilized eggs. Founder line 452 was established and crossed to the C57BL/6J inbred strain for 10 generations. Transgene expression is directed to lymphocytes.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 2 markers on Chromosomes 3 and 19 were found to be segregating for SJL, and one marker on Chromosome 2 was derived from an unknown source. This suggesting an incomplete backcross.

Expression Data

Expressed Gene	NFKB2, nuclear factor kappa B subunit 2, human
Site of Expression

Control Suggestions

Approximate Controls

Noncarrier
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Wang Z; Zhang B; Yang L; Ding J; Ding HF. 2008. Constitutive production of NF-kappaB2 p52 is not tumorigenic but predisposes mice to inflammatory autoimmune disease by repressing Bim expression. J Biol Chem 283(16):10698-706PubMed: 18281283 MGI: J:136017

View All References

Genetics

Tg(H2-K^b-NFKB2*)452Hfdg

Allele Symbol: Tg(H2-K^b-NFKB2*)452Hfdg

Allele Name	transgene insertion 452, Han-Fei Ding
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	NF-kB2 p52_452
Gene Symbol and Name	Tg(H2-K^b-NFKB2*)452Hfdg, transgene insertion 452, Han-Fei Ding
Gene Synonym(s)
Promoter	H2-K, histocompatibility 2, K region, mouse, laboratory
Expressed Gene	NFKB2, nuclear factor kappa B subunit 2, human
Strain of Origin	(C57BL/6J x SJL/J)F2
Chromosome	UN
Molecular Note	A transgenic construct containing the coding sequence for human NFKB p52 using a H2-K^b promoter and an immunoglobulin mu chain enhancer. Lines 434 and 452 were generated.
Mutations Made By	Han-Fei Ding, Georgia Health Sciences University

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- Inflammation
- Autoimmunity
  - anti-dsDNA antibodies

Mammalian Phenotype Terms by Genotype

References

Wang Z; Zhang B; Yang L; Ding J; Ding HF. 2008. Constitutive production of NF-kappaB2 p52 is not tumorigenic but predisposes mice to inflammatory autoimmune disease by repressing Bim expression. J Biol Chem 283(16):10698-706PubMed: 18281283 MGI: J:136017

Additional - Tg(H2-K^b-NFKB2*)452Hfdg related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Tg(H2-K-NFKB2*)

Breeding Considerations

While maintaining a live colony, these mice are bred as hemizygote male crossed to C57BL/6J female. The donating investigator has not tried to make this strain homozygous.

Additional Breeding and Husbandry Support

Citation
When using the STOCK Tg(H2-K^b-NFKB2*)452Hfdg/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36111 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Related Strains

All

By Allele

By Gene

By Collection

View All Strains

There are no related strains using this filter.

▲

Stock No: |

Related By:

▼

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tg(H2-Kb-NFKB2*)452Hfdg

Allele Symbol: Tg(H2-Kb-NFKB2*)452Hfdg

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Tg(H2-Kb-NFKB2*)452Hfdg related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Tg(H2-K^b-NFKB2*)452Hfdg

Allele Symbol: Tg(H2-K^b-NFKB2*)452Hfdg

Additional - Tg(H2-K^b-NFKB2*)452Hfdg related