B6.129X1-H2-Ab1^tm1Koni/J

Stock number: 013181
Product name: iab^neo
Strain synonyms: I-AB-flox
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These iab^neo floxed mutant mice possess a loxP-flanked neo cassette upstream of exon 1, and a single loxP site downstream of exon 1 of the H2-Ab1 locus. This floxed strain may be useful for studying MHC-II-restricted Ag presentation by B cells, macrophages, dendritic cell subsets, and other Ag presenting cells in vaccination, transplantation, allergy, and autoimmune disease studies.

Detailed description

These iab^neo floxed mutant mice possess a loxP-flanked neomycin resistance (neo) cassette upstream of the exon 1, and a single loxP site downstream of exon 1 of the histocompatibility 2, class II (MHC-II) antigen, beta 1 (H2-Ab1) locus. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, some of the resulting offspring will have exon 1 deleted in cre-expressing tissues. When bred with mice expressing Cre-recombinase driven by a cd19 promoter, iab deficiency results in the loss of MHC-II from the surface most B cells. This results in severely impaired T cell-dependent primary B cell antibody response upon immunization while exhibiting delayed kinetics in B cell germinal centers and memory B cell development. When bred with mice expressing Cre-recombinase driven by endothelial-specific receptor tyrosine kinase (Tek) promoter (see Stock No. 004128 for example), iab deficiency results in the loss of MHC-II from virtually all hematopoietic and endothelial cells. These mice produce their own CD4 T cells due to intact thymic MHC-II expression but have reduced numbers of forkhead box P3 (Foxp3)-expressing regulatory T cells. This floxed strain may be useful for studying MHC-II-restricted Ag presentation by B cells, macrophages, dendritic cell subsets, and other Ag presenting cells in vaccination, transplantation, allergy, and autoimmune disease studies.

Development

A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette upstream of the exon 1, and a single loxP site downstream of exon 1 of the histocompatibility 2, class II antigen, beta 1 (H2-Ab1) locus. The construct was electroporated into 129X1/SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with C57BL/6J mice. Resulting offspring were bred to C57BL/6J mice for at least 10 generations to establish a colony of iab^neo mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: H2-Ab1^tm1Koni
Name: targeted mutation 1, Pandelakis A Koni
MGI accession ID: MGI:2384629
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: H2-Ab1
Marker name: histocompatibility 2, class II antigen A, beta 1
Chromosome: 17
Strain of origin: 129X1/SvJ
Molecular note: A construct, in which the first coding exon was flanked by an upstream floxed neo cassette and a downstream loxP site, was integrated via homologous recombination. Flow cytometric analysis of splenocytes showed that the insertion of the loxP sites and neo cassette did not affect MHC-II surface expression.