B6.129S-Batf^tm1.1Kmm/J

Stock number: 013758
Product name: Batf^-
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research

Description

These knockout mice lack exons 1-2 of the Batf gene, abolishing gene function. This strain may be useful for studying T_H17 cells differentiation associated with Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.

Detailed description

These Batf^-/- mutant mice lack exons 1-2 of the basic leucine zipper transcription factor(Batf), ATF-like gene, abolishing gene function. Mice that are homozygous for this allele are viable and fertile. Batf is highly expressed in T helper (T_H) 1, T_H2 and T_H17 cells. Batf is required for the differentiation of interleukin (IL)-17-producing T_H17 cells which are CD4⁺ T cells that coordinate inflammatory responses in host defense. These mice exhibit normal T_H1 and T_H2 differentiation, but show a defect in T_H17 differentiation with a reduction in IL-17 production, but maintain normal levels of IL-2, interferon (IFN)-γ, and IL-10 under T_H17 conditions. Since T_H17 cells are the major pathogenic population in experimental autoimmune encephalomyelitis (EAE), these Batf^-/- mice are completely resistant EAE even when immunized with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG_35-55), a peptide known to cause demyelination associated with multiple sclerosis (MS) and EAE.

Development

A targeting vector was designed to replace exons 1-2 of the basic leucine zipper transcription factor, ATF-like (Batf) gene with a loxP-flanked neomycin resistance (neo) cassette. The construct was electroporated into 129S6/SvEvTac-derived EDJ22 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre expressing Adenovirus to delete the neo cassette. Resulting ES cells were injected into blastocysts and resulting chimeric males were bred with 129SvEv inbred females to establish a colony of Batf^-/- mice. The donating investigator stated that these mice were then backcrossed to C57BL/6 mice (see SNP note below) for at least 10 generations. 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.

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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

 

Allele

Symbol: Batf^tm1.1Kmm
Name: targeted mutation 1.1, Kenneth M Murphy
MGI accession ID: MGI:3851385
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Batf
Marker name: basic leucine zipper transcription factor, ATF-like
Chromosome: 12
Strain of origin: 129S6/SvEvTac
Molecular note: Exons 1 and 2 were replaced with a floxed neomycin cassette. The neomycin cassette was subsequently removed by transient expression of cre recombinase. No protein product was detected by immunoblot analysis of homozygote splenocyte or Th17 cells.