Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   17-NOV-11 Species laboratory mouse Generation N10pN1F6 (21-OCT-12) Generation Definitions   Donating Investigator Dr. Kenneth Murphy,   Washingston Univ School of Medicine

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.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Batf^tm1.1Kmm allele

013757	129S-Batftm1.1Kmm/J
013759	C.129S-Batftm1.1Kmm/J

View Strains carrying   Batf^tm1.1Kmm     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Batf^tm1.1Kmm/Batf^tm1.1Kmm

        129S/SvEv-Batf^tm1.1Kmm

• immune system phenotype
• abnormal CD4-positive T cell differentiation
  • culturing CD4⁺ T cells under Th17-polarizing conditions produces very few Th17 T cells   (MGI Ref ID J:150643)
• decreased interleukin-17 secretion
  • CD8⁺ T cells and lamina propia T cells fail to produce IL-17   (MGI Ref ID J:150643)
• decreased interleukin-21 secretion
  • CD4⁺ T cells cultured under Th17-polarizing conditions fail to produce IL-21   (MGI Ref ID J:150643)
• decreased susceptibility to experimental autoimmune encephalomyelitis
  • mice are completely resistant to EAE induced by MOG-peptide immunization   (MGI Ref ID J:150643)
  • T cells infiltrating the spinal cord of mice do not produce IL-17 after EAE induction in the manner that wild-type mice do   (MGI Ref ID J:150643)
• hematopoietic system phenotype
• abnormal CD4-positive T cell differentiation
  • culturing CD4⁺ T cells under Th17-polarizing conditions produces very few Th17 T cells   (MGI Ref ID J:150643)
• cellular phenotype
• abnormal CD4-positive T cell differentiation
  • culturing CD4⁺ T cells under Th17-polarizing conditions produces very few Th17 T cells   (MGI Ref ID J:150643)

View Research Applications

Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
      experimental allergic encephalomyelitis (EAE)
Immunodeficiency
      T cell deficiency

Neurobiology Research
Myelination Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Batftm1.1Kmm
Allele Name		targeted mutation 1.1, Kenneth M Murphy
Allele Type		Targeted (knock-out)
Mutation Made By		Dr. Kenneth Murphy,   Washingston Univ School of Medicine
Strain of Origin		129S/SvEv
Gene Symbol and Name		Batf, basic leucine zipper transcription factor, ATF-like
Chromosome		12
Gene Common Name(s)		B-ATF; BATF1; SFA-2; SFA2;
General Note		Embryonic stem cells = EDJ22
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. [MGI Ref ID J:150643]

Genotyping

Genotyping Information

Genotyping Protocols

Batf^tm1.1Kmm, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Schraml BU; Hildner K; Ise W; Lee WL; Smith WA; Solomon B; Sahota G; Sim J; Mukasa R; Cemerski S; Hatton RD; Stormo GD; Weaver CT; Russell JH; Murphy TL; Murphy KM. 2009. The AP-1 transcription factor Batf controls T(H)17 differentiation. Nature 460(7253):405-9. [PubMed: 19578362]  [MGI Ref ID J:150643]

Additional References

Batf^tm1.1Kmm related

Ciofani M; Madar A; Galan C; Sellars M; Mace K; Pauli F; Agarwal A; Huang W; Parkurst CN; Muratet M; Newberry KM; Meadows S; Greenfield A; Yang Y; Jain P; Kirigin FK; Birchmeier C; Wagner EF; Murphy KM; Myers RM; Bonneau R; Littman DR. 2012. A validated regulatory network for th17 cell specification. Cell 151(2):289-303. [PubMed: 23021777]  [MGI Ref ID J:188993]

Ise W; Kohyama M; Schraml BU; Zhang T; Schwer B; Basu U; Alt FW; Tang J; Oltz EM; Murphy TL; Murphy KM. 2011. The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells. Nat Immunol 12(6):536-43. [PubMed: 21572431]  [MGI Ref ID J:172119]

Tussiwand R; Lee WL; Murphy TL; Mashayekhi M; Wumesh KC; Albring JC; Satpathy AT; Rotondo JA; Edelson BT; Kretzer NM; Wu X; Weiss LA; Glasmacher E; Li P; Liao W; Behnke M; Lam SS; Aurthur CT; Leonard WJ; Singh H; Stallings CL; Sibley LD; Schreiber RD; Murphy KM. 2012. Compensatory dendritic cell development mediated by BATF-IRF interactions. Nature 490(7421):502-7. [PubMed: 22992524]  [MGI Ref ID J:188767]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   17-NOV-11
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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.

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