Overview

Also Known As:CIITA-

These Ciita knock-out mice lack expression of conventional MHC class II molecules on the surface of splenic B cells and dendritic cells.

Donating Investigator

Dr. Richard A. Flavell, Yale University School of Medicine

Genetic overview

Genetic Background	Generation

Ciita^tm1Ccum

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ciita	class II transactivator

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the targeted mutation are viable and fertile when housed under specific pathogen-free conditions. Mice do not express conventional MHC class II molecules on the surface of splenic B cells and dendritic cells. In addition, interferon gamma stimulated peritoneal macrophages and somatic tissues from homozygous mutant mice do not express MHC class II molecules. The levels of invarient chain and H2^m gene transcripts are substantially decreased in class II transactivator deficient mice. Homozygous mice have very few mature CD4 T cells in the periphery despite MHC class II expression in the thymus.

Control Suggestions

001026 BALB/cByJ

Additional Information

Considerations for Choosing Controls

Selected References

Fikrig E; Barthold SW; Chen M; Chang CH; Flavell RA. 1997. Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4+ T cells. J Immunol 159(11):5682-6PubMed: 9548512 MGI: J:109903

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Genetics

Ciita^tm1Ccum

Allele Symbol: Ciita^tm1Ccum

Allele Name	targeted mutation 1, Cheong-Hee Chang
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	C2ta^tm1Ccum; CIITA-; CIITA C^-; MHC classII^-
Gene Symbol and Name	Ciita, class II transactivator
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	16
Molecular Note	A genomic fragment containing exons which encode critical regions of the protein was replaced with a neomycin selection gene. Northern blot analysis on RNA derived from homozygous mice demonstrated that no detectable protein was produced from this allele.
Mutations Made By	Dr. Cheong-Hee Chang, Indiana University

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

MHC class II deficiency

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - MHC class II defects
  - MHC class II deficient
  - T cell deficiency
  - MHC class II associated invariant chain deficient
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - MHC class II defects
  - MHC class II associated invariant chain deficiency
  - T cell deficiency
Internal/Organ Research
- Lymphoid Tissue Defects
  - T cell deficiency

Genotype: Ciita^tm1Ccum related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - MHC class II defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Ciita^tm1Ccum/Ciita^tm1Ccum
involves: 129S2/SvPas * C57BL/6J

cellular phenotype

decreased T cell proliferation
- T cells proliferate poorly in response to keyhole limpet hemocyanin stimulation compared to wild-type

immune system phenotype

abnormal B cell physiology
- the expression of IL-10 after stimulation with LPS of IL-4 for 3 days is enhanced in mutant B cells by about 2-3 fold

abnormal CD4-positive, alpha-beta T cell physiology
- CD4+ T cell responses are significantly reduced to allogeneic stimulation
- when day 16 fetal liver cells are transferred into wild-type mice, CD4+ T cell development is normal and when wild-type fetal cells are transferred into homozygotes, CD4+ T cells fail to mature

abnormal cytokine secretion
- spleen and lymph node cells produced no measurable cytokines at 8 weeks after infection

abnormal dendritic cell physiology
- Bone marrow-derived mutant dendritic cells in culture differentiate in response to GM-CSF despite absence of MHC class II molecules; however, when stimulated with LPS of CpG display about a 2-fold increase in IL-10 expression compared to wild-type

abnormal level of surface class II molecules
- bone marrow-derived dendritic cells do not express MHC class II molecules
- MHC class II molecules are not detected in organs of mutants, except for interdigitating reticular cells where expression is not induced by interferon-gamma injection

abnormal lymphocyte physiology

abnormal MHC II cell surface expression on macrophages
- macrophages do not express MHC II cell surface expression on interferon-gamma stimulation

abnormal popliteal lymph node morphology
- total numbers of cells in lymph nodes of null increased only slightly after infection with L. amazonensis compared with an 8-fold increase in size of wild-type

abnormal T cell differentiation

abnormal T cell physiology

altered susceptibility to infection

decreased CD4-positive, alpha beta T cell number
- mice have reduced numbers of mature CD4+ T cells in the periphery

decreased susceptibility to parasitic infection
- after infection with L. amazonensis, infected cells contained tightly packed organisms with few parasitophorous vacuole visible whereas infected macrophages in wild-type mice contained only a few organisms which are preferentially located at the edge of parasitophorous vacuoles
- after infection with L. Amazonensis, mice show no lesion development up to 11 weeks post infection, reduced cellular infiltration, lower parasite load and few cells in the popliteal lymph nodes draining the foot
- arasitophorous vacuoles

decreased T cell proliferation
- T cells proliferate poorly in response to keyhole limpet hemocyanin stimulation compared to wild-type

increased CD4-positive, alpha beta T cell number
- in spleen cells, there is a 4.5-fold increase of CD4+CD69^high cells in mutants at 8 weeks after parasite infection

increased CD8-positive, alpha-beta T cell number
- in spleen cell, a slight increase in the number of CD8+ T cells compared to wild-type is seen pre- and post-infection

increased susceptibility to parasitic infection
- lesions become significantly larger with higher parasitic burdens 16 weeks after infection with L. major, compared to eventual lesion resolution in wild-type mice

hematopoietic system phenotype

abnormal B cell physiology
- the expression of IL-10 after stimulation with LPS of IL-4 for 3 days is enhanced in mutant B cells by about 2-3 fold

abnormal CD4-positive, alpha-beta T cell physiology
- CD4+ T cell responses are significantly reduced to allogeneic stimulation
- when day 16 fetal liver cells are transferred into wild-type mice, CD4+ T cell development is normal and when wild-type fetal cells are transferred into homozygotes, CD4+ T cells fail to mature

abnormal lymphocyte physiology

abnormal MHC II cell surface expression on macrophages
- macrophages do not express MHC II cell surface expression on interferon-gamma stimulation

abnormal T cell differentiation

abnormal T cell physiology

decreased CD4-positive, alpha beta T cell number
- mice have reduced numbers of mature CD4+ T cells in the periphery

decreased T cell proliferation
- T cells proliferate poorly in response to keyhole limpet hemocyanin stimulation compared to wild-type

increased CD4-positive, alpha beta T cell number
- in spleen cells, there is a 4.5-fold increase of CD4+CD69^high cells in mutants at 8 weeks after parasite infection

increased CD8-positive, alpha-beta T cell number
- in spleen cell, a slight increase in the number of CD8+ T cells compared to wild-type is seen pre- and post-infection

Genotype: Ciita^tm1Ccum/Ciita^tm1Ccum
involves: 129S2/SvPas * C57BL/6

immune system phenotype

abnormal level of surface class II molecules
- class II expression is absent on CD11c⁺ dendritic cells
- class II surface expression in the cortex and medulla of the thymus is very patchy
- unactivated or activated B cells do not express class II on the surface

References

Fikrig E; Barthold SW; Chen M; Chang CH; Flavell RA. 1997. Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4+ T cells. J Immunol 159(11):5682-6PubMed: 9548512 MGI: J:109903

Additional - Ciita^tm1Ccum related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Ciita Alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

Homozygous mice are viable and fertile. When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to BALB/cByJ inbred mice (Stock No. 001026). Alternatively, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the CIITA- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003238 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 or Wild-type for Ciita<tm1Ccum>

Related Products and Services

Frozen Mouse Embryo	C.129S2(B6)-Ciita<tm1Ccum>/J	$2595.00
Frozen Mouse Embryo	C.129S2(B6)-Ciita<tm1Ccum>/J	$2595.00
Frozen Mouse Embryo	C.129S2(B6)-Ciita<tm1Ccum>/J	$3373.50
Frozen Mouse Embryo	C.129S2(B6)-Ciita<tm1Ccum>/J	$3373.50

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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. 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

Licensing Information

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Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

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Also Known As:CIITA-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Additional Information

Selected References

Ciitatm1Ccum

Allele Symbol: Ciitatm1Ccum

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Genotype: Ciitatm1Ccum related

Mammalian Phenotype Terms by Genotype

Genotype: Ciitatm1Ccum/Ciitatm1Ccuminvolves: 129S2/SvPas * C57BL/6J

cellular phenotype

immune system phenotype

hematopoietic system phenotype

Genotype: Ciitatm1Ccum/Ciitatm1Ccuminvolves: 129S2/SvPas * C57BL/6

immune system phenotype

References

Additional - Ciitatm1Ccum 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

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Ciita^tm1Ccum

Allele Symbol: Ciita^tm1Ccum

Genotype: Ciita^tm1Ccum related

Genotype: Ciita^tm1Ccum/Ciita^tm1Ccum
involves: 129S2/SvPas * C57BL/6J

Genotype: Ciita^tm1Ccum/Ciita^tm1Ccum
involves: 129S2/SvPas * C57BL/6

Additional - Ciita^tm1Ccum related