Overview

Also Known As:Batf3^-

These knockout mice have a loxP-flanked neomycin resistance cassette replacing exons 1-2 of the Batf3) gene, abolishing gene function. This strain may be useful for studying CD8 deficiency, antigen cross-presentation, and CD8^- T cell responses against viral infection and responses to tumor challenge.

Donating Investigator

Dr. Kenneth Murphy, Washington University School of Medicine

Genetic overview

Genetic Background	Generation

Batf3^tm1Kmm

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Batf3	basic leucine zipper transcription factor, ATF-like 3

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Virology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These Batf3^-/- knockout mice have a loxP-flanking neomycin (neo) resistance cassette replacing exons 1-2 of the basic leucine zipper transcription factor, ATF-like 3 (Batf3) gene, abolishing gene function. Mice that are homozygous for this allele are viable and fertile. Batf3 is highly expressed in CD11c⁺ CD8α⁺ conventional dendritic cells (cDCs), with low to absent expression in other immune cells.The deletion of Batf3 prevents development of splenic CD8α⁺ cDCs, which are important for cross-presentation during infections. Lymph nodes and thymi of Batf3^-/- mice lack CD8α⁺ DCs, and DCs generated from Batf3^-/- bone marrow (BM) and spleens are deficient in Toll-like receptor (TLR) 3-induced interleukin (IL)-12 production. These mice also lack CD103⁺CD11b^- DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Exhibiting defects in CD8⁺T cell response priming, including lack of virus-specific responses, results in the inability to reject highly immunogenic syngeneic tumors. .

Development

A targeting vector was designed to replace exons 1-2 of the basic leucine zipper transcription factor, ATF-like 3 (Batf3) gene with a loxP-flanked neomycin resistance (neo) cassette. The construct was electroporated into 129S6/SvEvTac-derived MC50 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred to 129SvEv females to establish a colony. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation to establish the colony.

Control Suggestions

Approximate Controls

002448 129S1/SvImJ

Additional Information

Considerations for Choosing Controls

Selected References

Hildner K; Edelson BT; Purtha WE; Diamond M; Matsushita H; Kohyama M; Calderon B; Schraml BU; Unanue ER; Diamond MS; Schreiber RD; Murphy TL; Murphy KM. 2008. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322(5904):1097-100PubMed: 19008445 MGI: J:141064

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Genetics

Batf3^tm1Kmm

Allele Symbol: Batf3^tm1Kmm

Allele Name	targeted mutation 1, Kenneth M Murphy
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Batf3, basic leucine zipper transcription factor, ATF-like 3
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	1
Molecular Note	Exons 1-2 were replaced by a floxed neomycin cassette. Cre-mediated recombination removed the neo cassette. Gene inactivation was confirmed by a lack of protein detected by immunoblot analysis of Th1 CD4⁺ T cells.
Mutations Made By	Dr. Kenneth Murphy, Washington University School of Medicine

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
- Growth Factors/Receptors/Cytokines
- Immunodeficiency
  - specific T cell deficiency
  - T cell deficiency
- Lymphoid Tissue Defects
  - B and T cell deficiency
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
Virology Research
- B and T Cell Deficiency

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Batf3^tm1Kmm/Batf3^tm1Kmm
involves: 129S6/SvEvTac

hematopoietic system phenotype

abnormal cytotoxic T cell physiology
- reduced cytotoxic T cell response to anti-Clec9a coupled antigen

immune system phenotype

abnormal cytotoxic T cell physiology
- reduced cytotoxic T cell response to anti-Clec9a coupled antigen

mammalian phenotype

immune system phenotype
- Normal - homozygotes retain an enhanced antibody response to anti-Clec9a coupled antigen

Genotype: Batf3^tm1Kmm/Batf3^tm1Kmm
involves: 129S6/SvEvTac * BALB/cJ

immune system phenotype

abnormal dendritic cell differentiation
- bone marrow chimera experiments indicate a lack of CD8a⁺ DCs is due to a cell-intrinsic effect of the mutant locus
- mice lack CD8a⁺ dendritic cell subsets
- in vitro bone marrow differentiation cultures fail to generate CD24⁺ Sirp-alpha^- DCs that are similar to CD8a⁺ DC

abnormal dendritic cell physiology
- conventional DCs fail to secrete IL-12 after TL3 stimulation but have normal responses to TLR4 and TLR9 stimulation

abnormal dendritic cell antigen presentation
- conventional DCs are unable to cross-present (i.e. take up protein, process into peptide and present) ovalbumin antigen to ova-specific CD8⁺ T cells

decreased myeloid dendritic cell number
- mice have a loss of CD11c^hiCD11b^dull DCs and CD11c^hi CD8a⁺CD24⁺ DCs
- lymph nodes and thymi lack CD8a⁺ DC subsets
- mice have normal populations of CD4⁺ and CD8a-CD4- conventional DC subsets
- mice lack splenic CD11c^hiCD8a⁺DEC205⁺ dendritic cells
- CD103-⁺DEC205⁺CD8a^-CD11b^lo/- dermal DC numbers are reduced 5-fold in draining lymph nodes of the skin

abnormal cytotoxic T cell physiology
- CD8⁺ T cells from mice infected with West Nile virus (WNV) have defective IFN-gamma secretion when cultured with WNV-peptide
- infiltrating CD8⁺ T cells fail to infiltrate transplanted syngenic tumors
- bone marrow chimera studies demonstrate that defective cytolytic activity is not intrinsic to the CD8⁺ T cells but rather defective dendritic cell function

decreased cytotoxic T cell cytolysis
- CD8⁺ T cells from mice infected with West Nile virus (WNV) have defective killing of WNV peptide-loaded target cells

decreased memory T cell number
- mice fail to develop West Nile Virus (WNV)-specific memory CD8⁺ T cells after infection with the virus
- the number of CD8⁺CD44^hiCD62L^lowcells memory cells is about half-that of wild-type mice before infection and is five-fold less after infection

abnormal immune system physiology
- transplanted syngenic fibrosarcomas grow in size instead of being reapidly rejected as happens in control mice

cellular phenotype

abnormal dendritic cell differentiation
- mice lack CD8a⁺ dendritic cell subsets
- bone marrow chimera experiments indicate a lack of CD8a⁺ DCs is due to a cell-intrinsic effect of the mutant locus
- in vitro bone marrow differentiation cultures fail to generate CD24⁺ Sirp-alpha^- DCs that are similar to CD8a⁺ DC

hematopoietic system phenotype

abnormal cytotoxic T cell physiology
- infiltrating CD8⁺ T cells fail to infiltrate transplanted syngenic tumors
- CD8⁺ T cells from mice infected with West Nile virus (WNV) have defective IFN-gamma secretion when cultured with WNV-peptide
- bone marrow chimera studies demonstrate that defective cytolytic activity is not intrinsic to the CD8⁺ T cells but rather defective dendritic cell function

decreased myeloid dendritic cell number
- mice lack splenic CD11c^hiCD8a⁺DEC205⁺ dendritic cells
- CD103-⁺DEC205⁺CD8a^-CD11b^lo/- dermal DC numbers are reduced 5-fold in draining lymph nodes of the skin
- mice have a loss of CD11c^hiCD11b^dull DCs and CD11c^hi CD8a⁺CD24⁺ DCs
- lymph nodes and thymi lack CD8a⁺ DC subsets
- mice have normal populations of CD4⁺ and CD8a-CD4- conventional DC subsets

decreased cytotoxic T cell cytolysis
- CD8⁺ T cells from mice infected with West Nile virus (WNV) have defective killing of WNV peptide-loaded target cells

decreased memory T cell number
- mice fail to develop West Nile Virus (WNV)-specific memory CD8⁺ T cells after infection with the virus
- the number of CD8⁺CD44^hiCD62L^lowcells memory cells is about half-that of wild-type mice before infection and is five-fold less after infection

abnormal dendritic cell differentiation
- bone marrow chimera experiments indicate a lack of CD8a⁺ DCs is due to a cell-intrinsic effect of the mutant locus
- in vitro bone marrow differentiation cultures fail to generate CD24⁺ Sirp-alpha^- DCs that are similar to CD8a⁺ DC
- mice lack CD8a⁺ dendritic cell subsets

References

Hildner K; Edelson BT; Purtha WE; Diamond M; Matsushita H; Kohyama M; Calderon B; Schraml BU; Unanue ER; Diamond MS; Schreiber RD; Murphy TL; Murphy KM. 2008. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322(5904):1097-100PubMed: 19008445 MGI: J:141064

Additional - Batf3^tm1Kmm related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Batf3 Alternate1
- Standard PCR:Batf3
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the Batf3^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #013596 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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Batf3<tm1Kmm>

Related Products and Services

Frozen Mouse Embryo	129S-Batf3<tm1Kmm>/J	$2595.00
Frozen Mouse Embryo	129S-Batf3<tm1Kmm>/J	$2595.00
Frozen Mouse Embryo	129S-Batf3<tm1Kmm>/J	$3373.50
Frozen Mouse Embryo	129S-Batf3<tm1Kmm>/J	$3373.50

Payment Terms and Conditions

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.

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

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Batf3-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Batf3tm1Kmm

Allele Symbol: Batf3tm1Kmm

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Batf3tm1Kmm/Batf3tm1Kmminvolves: 129S6/SvEvTac

hematopoietic system phenotype

immune system phenotype

mammalian phenotype

Genotype: Batf3tm1Kmm/Batf3tm1Kmminvolves: 129S6/SvEvTac * BALB/cJ

immune system phenotype

cellular phenotype

hematopoietic system phenotype

References

Additional - Batf3tm1Kmm related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Also Known As:Batf3^-

Batf3^tm1Kmm

Allele Symbol: Batf3^tm1Kmm

Genotype: Batf3^tm1Kmm/Batf3^tm1Kmm
involves: 129S6/SvEvTac

Genotype: Batf3^tm1Kmm/Batf3^tm1Kmm
involves: 129S6/SvEvTac * BALB/cJ

Additional - Batf3^tm1Kmm related