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

Stock number: 017328
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

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.

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.

Allele

Symbol: Tg(H2-K^b-NFKB2*)452Hfdg
Name: transgene insertion 452, Han-Fei Ding
MGI accession ID: MGI:5141614
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(H2-K^b-NFKB2*)452Hfdg
Marker name: transgene insertion 452, Han-Fei Ding
Chromosome: UN
Strain of origin: (C57BL/6J x SJL/J)F2
Expressed genes: NFKB2,nuclear factor kappa B subunit 2,human
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.