Overview

Also Known As:H2-Mα-

These H2-DMa knock-out mice exhibit defects in immunological responses.

Donating Investigator

Luc van Kaer, Vanderbilt University School of Medicine

Genetic overview

Genetic Background	Generation

H2-DMa^tm1Luc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	H2-DMa	histocompatibility 2, class II, locus DMa

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools

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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 H2-DMa^tm1Luc targeted mutation are viable and fertile but generally smaller than wildtype siblings. Defects in immunological responses in homozygous mutant mice include defects in loading of peptides into the MHC class II molecules, presentation of antigen in a MHC class II restricted manner, and intrathymic T-cell positive and negative selection. This strain may be useful as a model for examination of MHC class II restricted antigen presentation, tissue graft rejection, and T-cell repertoire selection.

Development

This strain was developed in the laboratory of Dr. Luc Van Kaer at Vanderbilt University School of Medicine. The 129-derived J1 ES cell line was used. A 1.5kb piece of the H2-DMa gene from all of exon 1 and most of exon 2 was replaced with a vector containing the neomycin resistance gene.

Control Suggestions

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Martin WD; Hicks GG; Mendiratta SK; Leva HI; Ruley HE; Van Kaer L. 1996. H2-M mutant mice are defective in the peptide loading of class II molecules, antigen presentation, and T cell repertoire selection. Cell 84(4):543-50PubMed: 8598041 MGI: J:31625

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Genetics

H2-DMa^tm1Luc

Allele Symbol: H2-DMa^tm1Luc

Allele Name	targeted mutation 1, Luc van Kaer
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	H2-DM-; H-2M-; H2-M-; H2-M⁰; H2-Malpha^-
Gene Symbol and Name	H2-DMa, histocompatibility 2, class II, locus DMa
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	17
Molecular Note	A neomycin resistance cassette replaced a 1.5 kb fragment of the gene, encompassing the first and most of the second exon.
Mutations Made By	Dr. Luc Van Kaer, Vanderbilt University School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: H2-DMa^tm1Luc related

Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
- Immunodeficiency
  - MHC class II defects
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: H2-DMa^tm1Luc/H2-DMa^tm1Luc
B6.129S4-H2-Dma

hematopoietic system phenotype

abnormal T-helper 1 physiology
- in vivo, Th1 response to MOG or PLP is reduced compared to in wild-type mice

immune system phenotype

decreased susceptibility to experimental autoimmune encephalomyelitis
- PLP-treated mice fail to develop EAE unlike similarly treated wild-type mice
- Normal - however, MOG-primed are capable of inducing encephalomyelitis in a wild-type host
- whether MOG-primed or adoptively transferred with MOG-specific T blasts, mice fail to develop symptoms of experimental autoimmune encephalomyelitis (EAE) unlike wild-type mice

abnormal T-helper 1 physiology
- in vivo, Th1 response to MOG or PLP is reduced compared to in wild-type mice

decreased susceptibility to type IV hypersensitivity reaction
- slightly compared to in wild-type mice when wild-type MOG T cells are transferred

abnormal antigen presentation
- antigen presenting cells cannot process and present recombinant MOG protein unlike wild-type cells

Genotype: H2-DMa^tm1Luc/H2-DMa^tm1Luc
involves: 129S4/SvJae

growth/size/body region phenotype

decreased body size
- smaller than control littermates

mortality/aging

premature death
- mutants occasionally die without evidence of severe infection

hematopoietic system phenotype

abnormal positive T cell selection
- CD4+ T cell-selection is almost completely abrogated in lethally irradiated hosts upon transfer of transgenic bone marrow

decreased CD4-positive, alpha beta T cell number
- decreased number of peripheral CD4+ T cells
- reduced numbers of CD4+CD8- T cells

abnormal CD4-positive, alpha-beta T cell physiology
- CD4+CD8- T cells exhibit altered reactivity to antigen-presenting cells from a variety of mouse strains

immune system phenotype

abnormal antigen presentation via MHC class II
- reduced ability to present exogenous peptides
- inability to present intact protein antigen to class II-restricted T cells

abnormal positive T cell selection
- CD4+ T cell-selection is almost completely abrogated in lethally irradiated hosts upon transfer of transgenic bone marrow

abnormal level of surface class II molecules
- abnormal level of surface class II molecules on B cells

decreased interferon-gamma secretion
- decreased interferon gamma production

increased susceptibility to bacterial infection
- increased susceptibility to Leishmania major infection
- by 17 weeks, mice have developed large (>4mm) non-healing footpad lesions, whereas controls do not show lesions larger than 4mm

abnormal CD4-positive, alpha-beta T cell physiology
- CD4+CD8- T cells exhibit altered reactivity to antigen-presenting cells from a variety of mouse strains

decreased CD4-positive, alpha beta T cell number
- decreased number of peripheral CD4+ T cells
- reduced numbers of CD4+CD8- T cells

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

Genotype: H2-DMa^tm1Luc/H2-DMa^tm1Luc
involves: 129S4/SvJae * C57BL/6

immune system phenotype

abnormal antigen presentation
- splenic antigen presenting cells (APCs) can present an encephalitogenic MOG peptide P35-55 to I-A^b-restricted p35-55-specific T cells but a one log-higher concentration of peptide is needed to stimulate proliferation, compared to wild-type or Cd74 deficient cells; mutant APCs are ineffective at presenting intact MOG to T cells compared with wild-type APCs, suggesting that processing is required for presentation of intact MOG
- d74 deficient cells; mutant APCs are ineffective at presenting intact MOG to T cells compared with wild-type APCs, suggesting that processing is required for presentation of intact MOG

decreased susceptibility to experimental autoimmune encephalomyelitis
- adoptive transfer of wild-type encephalitogenic T cells does not induce EAE in mutant recipients
- mice do not develop experimental autoimmune encephalitis (EAE) upon direct immunization with p35-55 while wild-type mice do develop EAE

References

Martin WD; Hicks GG; Mendiratta SK; Leva HI; Ruley HE; Van Kaer L. 1996. H2-M mutant mice are defective in the peptide loading of class II molecules, antigen presentation, and T cell repertoire selection. Cell 84(4):543-50PubMed: 8598041 MGI: J:31625

Additional References

Dorfman JR; Stefanova I; Yasutomo K; Germain RN. 2000. CD4+ T cell survival is not directly linked to self-MHC-induced TCR signaling. Nat Immunol 1(4):329-35PubMed: 11017105 MGI: J:65116
Honey K; Forbush K; Jensen PE; Rudensky AY. 2004. Effect of decreasing the affinity of the class II-associated invariant chain peptide on the MHC class II peptide repertoire in the presence or absence of H-2M. J Immunol 172(7):4142-50PubMed: 15034026 MGI: J:88717

Additional - H2-DMa^tm1Luc related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:H2-DMa
- Genotyping resources and troubleshooting
Breeding Considerations

Mice homozygous for the H2-Ma^tm1Luc targeted mutation are viable and fertile but generally smaller than wildtype siblings. When maintaining a live colony, homozygous mice may be bred together. The expected coat color from breeding is black.
- Additional Breeding and Husbandry Support
Appearance
- black
  Related Genotype: a/a
Citation
When using the H2-Mα- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002643 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 DMa<tm1Luc>

Related Products and Services

Frozen Mouse Embryo	B6;129S4-H2-DMa<tm1Luc>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6;129S4-H2-DMa<tm1Luc>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6;129S4-H2-DMa<tm1Luc>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6;129S4-H2-DMa<tm1Luc>/J Frozen Embryos	$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

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:H2-Mα-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

H2-DMatm1Luc

Allele Symbol: H2-DMatm1Luc

Disease Terms

Research Areas By Phenotype

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

Genotype: H2-DMatm1Luc related

Mammalian Phenotype Terms by Genotype

Genotype: H2-DMatm1Luc/H2-DMatm1LucB6.129S4-H2-Dma

hematopoietic system phenotype

immune system phenotype

Genotype: H2-DMatm1Luc/H2-DMatm1Lucinvolves: 129S4/SvJae

growth/size/body region phenotype

mortality/aging

hematopoietic system phenotype

immune system phenotype

Genotype: H2-DMatm1Luc/H2-DMatm1Lucinvolves: 129S4/SvJae * C57BL/6

immune system phenotype

References

Additional References

Additional - H2-DMatm1Luc related

Genotyping Protocols

Breeding Considerations

Appearance

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

H2-DMa^tm1Luc

Allele Symbol: H2-DMa^tm1Luc

Genotype: H2-DMa^tm1Luc related

Genotype: H2-DMa^tm1Luc/H2-DMa^tm1Luc
B6.129S4-H2-Dma

Genotype: H2-DMa^tm1Luc/H2-DMa^tm1Luc
involves: 129S4/SvJae

Genotype: H2-DMa^tm1Luc/H2-DMa^tm1Luc
involves: 129S4/SvJae * C57BL/6

Additional - H2-DMa^tm1Luc related