Overview

Also Known As:CD74-

These Cd74 (formerly Ii) knock-out mice lack the invariant chain associated with major histocompatibility complex (MHC) class II molecules with a reduction in surface class II molecules.

Donating Investigator

Dr. Elizabeth Bikoff, University of Oxford.

Genetic overview

Genetic Background	Generation

Cd74^tm1Liz

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Cd74	CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated)

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Research Applications

Research Tools
Immunology, Inflammation and Autoimmunity 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 Ii^tm1Liz targeted mutation are viable and fertile. The phenotype exhibited by mutant mice lacking the Ii (Ia-associated invariant chain) gene product is appreciably influenced by genetic background. As expected in BALB/cAn-Iitm1Liz mice, class II surface expression is markedly decreased. However, discordant expression of class II conformational epitopes is not detected, indicating that the few class II molecules present are properly folded and possess a normal configuration. Although spleen cells are ineffective for presentation of intact protein antigens, they show consistently superior peptide-loading capabilities. Thus surface class II molecules appear empty or occupied by easily displaced peptide(s). B lymphocyte development appears defective particularly in lymph node populations. Mature splenic dendritic cells in Ii chain mutants also display reduced class II surface expression. Thymi contain 3-fold fewer CD4+ T lymphocytes, but maturation of CD4+ T cells in the periphery occurs at near normal levels and secondary proliferative responses are elicited upon peptide challenge.

Control Suggestions

Approximate Controls

001026 BALB/cByJ

Additional Information

Considerations for Choosing Controls

Selected References

Bikoff EK; Germain RN; Robertson EJ. 1995. Allelic differences affecting invariant chain dependency of MHC class II subunit assembly. Immunity 2(3):301-10PubMed: 7697546 MGI: J:109917

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Genetics

Cd74^tm1Liz

Allele Symbol: Cd74^tm1Liz

Allele Name	targeted mutation 1, Elizabeth K Bikoff
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Ii^-; Ii^tm1Liz; MHCII^-
Gene Symbol and Name	Cd74, CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated)
Gene Synonym(s)
Strain of Origin	129S/SvEv-Gpi1^c
Chromosome	18
Molecular Note	A MC1neopA cassette replaced the first intron and 11 nucleotides of the second exon.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Cd74^tm1Liz related

Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - MHC class II defects
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - 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: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv * C57BL/6J

cellular phenotype

decreased T cell proliferation
- immunization with p35-55 does not induce significant T cell proliferation compared to wild-type cells

growth/size/body region phenotype

cachexia
- occasionally, homozygotes display symptoms of severe wasting

decreased body size
- homozygotes are usually smaller than littermates

hematopoietic system phenotype

decreased CD4-positive, alpha beta T cell number
- mutants have decreased numbers of CD4+8- TCRhi T cells in the thymus
- number of CD4+CD8- T cells in the periphery; decreased numbers of mature CD4+ T lymphocytes are seen in analyses of splenic T cells

decreased T cell proliferation
- immunization with p35-55 does not induce significant T cell proliferation compared to wild-type cells

immune system phenotype

abnormal antigen presentation
- compared with wild-type APCs, suggesting that processing is required for presentation of intact MOG
- splenic antigen presenting cells (APCs) present an encephalitogenic MOG peptide p35-55 to I-A^b-restricted p35-55-specific T cells equivalently to wild-type APCs, stimulating proliferation but are ineffective at presenting intact MOG to T cells compared with wild-type APCs, suggesting that processing is required for presentation of intact MOG

abnormal antigen presentation via MHC class II
- mutant spleen cells stimulated stronger responses in presence of already processed peptides hen egg lysozyme (HEL) 74-88 and Ealpha 52-68, but fail to present native protein antigens keyhole limpet cyanin (KLH) and IgG2a

abnormal level of surface class II molecules
- mutant spleen cells exhibit reduced levels of I-A^b surface antigen compared to wild-type spleen cells

decreased CD4-positive, alpha beta T cell number
- mutants have decreased numbers of CD4+8- TCRhi T cells in the thymus
- number of CD4+CD8- T cells in the periphery; decreased numbers of mature CD4+ T lymphocytes are seen in analyses of splenic T cells

decreased interferon-gamma secretion
- immunization with p35-55 does not induce Ifng secretion indicating inability to prime p35-55 specific CD4+ T cells

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

decreased T cell proliferation
- immunization with p35-55 does not induce significant T cell proliferation compared to wild-type cells

defective assembly of class II molecules
- class II molecules produced by mutants show enhanced peptide binding compared to wild-type; molecules behave as if empty or occupied by easily displaced peptide in contrast to wild-type cells that are stably occupied with self and serum-derived peptides
- majority of class II molecules are comprised of immature alpha and beta chains that have not been exported past the cis-Golgi
- mutant spleen cells show significantly reduced amounts of alpha/beta heterodimers associated with the invariant chain; increased amounts of free alpha and beta chains are present
- no mature compact SDS-resistant alpha/beta heterodimers (I-A^b) are produced by mutant spleens in contrast to wild-type cells

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
B6.129S-Cd74

cellular phenotype

decreased T cell proliferation
- lymph node cells show significantly lower proliferative responses to immunization with keyhole limpet cyanin (KLH) compared to wild-type

hematopoietic system phenotype

abnormal T-helper 1 physiology
- in vitro, lymph node cells from mice receiving wild-type MOG T cells exhibit reduced Th1 recall response compared with similarly treated wild-type mice
- in vitro, the frequency of Th1 recall response is greater than in H2-Dma^tm1Luc homozygotes
- in vivo, Th1 response to MOG is absent unlike in wild-type mice
- in vivo, Th1 response to PLP is reduced compared to in wild-type mice

decreased CD4-positive, alpha beta T cell number
- significant reduction in numbers of mature CD4+CD8- thymocytes in thymus and periphery is seen compared to wild-type

decreased T cell proliferation
- lymph node cells show significantly lower proliferative responses to immunization with keyhole limpet cyanin (KLH) compared to wild-type

immune system phenotype

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

abnormal antigen presentation via MHC class II
- class II molecules are relatively ineffective for presentation of native protein antigens

abnormal level of surface class II molecules
- mutants expressed greatly reduced amounts of class II on spleen cells compared to wild-type

abnormal T-helper 1 physiology
- in vitro, lymph node cells from mice receiving wild-type MOG T cells exhibit reduced Th1 recall response compared with similarly treated wild-type mice
- in vitro, the frequency of Th1 recall response is greater than in H2-Dma^tm1Luc homozygotes
- in vivo, Th1 response to MOG is absent unlike in wild-type mice
- in vivo, Th1 response to PLP is reduced compared to in wild-type mice

decreased CD4-positive, alpha beta T cell number
- significant reduction in numbers of mature CD4+CD8- thymocytes in thymus and periphery is seen compared to wild-type

decreased susceptibility to experimental autoimmune encephalomyelitis
- PLP-treated mice fail to develop EAE unlike similarly treated wild-type mice
- 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

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

decreased T cell proliferation
- lymph node cells show significantly lower proliferative responses to immunization with keyhole limpet cyanin (KLH) compared to wild-type

defective assembly of class II molecules
- in spleen cells, immature alpha and beta chains exhibiting no evidence of having been exported past the cis-Golgi are observed, whereas compact alpha/beta dimers efficiently transported past the cis-Golgi are produced by Cd74^tm2Liz-deficient cells; floppy conformers are seen, compared to compact dimers in wild-type
- lls; floppy conformers are seen, compared to compact dimers in wild-type

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv * C57BL/6

immune system phenotype

abnormal antigen presentation via MHC class II
- mutants display isotype-specific antigen presentation defects; MHC A^k-restricted antigen presentation is reduced compared to wild-type

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv * BALB/cAn

hematopoietic system phenotype

abnormal B cell differentiation
- B cell maturation is defective

decreased CD4-positive, alpha beta T cell number
- mutant thymi display 3-fold fewer mature CD4+ T cells compared to wild-type; spleen and lymph node CD4+ T cell percentages are reduced ~2-fold
- T cells carrying Vbeta (VB) segments (VB3, 5, 11 and 12) are well represented whereas they are completely eliminated in wild-type BALB/c controls, suggesting a role during presentation of endogenous superantigens

increased immature B cell number
- higher percentages of immature B cells lacking surface IgD and CD23 expression

immune system phenotype

abnormal antigen presentation via MHC class II
- antigen presentation by mutant spleen cells to E^drestricted T cell clones is substantially decreased
- E^drestricted T cells show enhanced activity when challenged with endogenously process beta 2 microglobulin (B2m) epitopes in presence of mutant splenocytes
- mutant spleen cells on an H-2^d background show enhanced peptide-loading capabilities over wild-type cells
- spleen cells are ineffective for presentation of intact protein antigen as opposed to processed peptide antigens
- spleen cells effectively function as stimulators for allogeneic T cells, eliciting strong mixed lymphocyte responses
- T cell hybridomas produce Il-2 and T cell lines proliferate when stimulated by mutant spleen cells; similar results are seen using T cell clones specific for peptides including ovalbumin (OVA)_323-339 and IgG2a^b

abnormal B cell differentiation
- B cell maturation is defective

abnormal dendritic cell antigen presentation
- dendritic cells show reduced class II surface expression in overnight culture compared to wild-type

abnormal professional antigen presenting cell physiology
- splenocytes display enhanced binding capabilities

decreased CD4-positive, alpha beta T cell number
- mutant thymi display 3-fold fewer mature CD4+ T cells compared to wild-type; spleen and lymph node CD4+ T cell percentages are reduced ~2-fold
- T cells carrying Vbeta (VB) segments (VB3, 5, 11 and 12) are well represented whereas they are completely eliminated in wild-type BALB/c controls, suggesting a role during presentation of endogenous superantigens

increased immature B cell number
- higher percentages of immature B cells lacking surface IgD and CD23 expression

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv * BALB/c * C57BL

cellular phenotype

abnormal T cell proliferation
- proliferative responses to intact hen egg lysozyme (HEL) protein antigen are reduced in mutants, but immunized mice challenged secondarily with HEL_46-61 peptide show similar response to wild-type mice

hematopoietic system phenotype

abnormal B cell differentiation
- B cell maturation is defective

abnormal T cell proliferation
- proliferative responses to intact hen egg lysozyme (HEL) protein antigen are reduced in mutants, but immunized mice challenged secondarily with HEL_46-61 peptide show similar response to wild-type mice

increased immature B cell number
- higher percentages of immature B cells lacking surface IgD and CD23 expression

immune system phenotype

abnormal antigen presentation via MHC class II
- spleen cells effectively function as stimulators for allogeneic T cells, eliciting strong mixed lymphocyte responses

abnormal B cell differentiation
- B cell maturation is defective

abnormal dendritic cell antigen presentation
- dendritic cells show reduced class II surface expression in overnight culture compared to wild-type

abnormal T cell proliferation
- proliferative responses to intact hen egg lysozyme (HEL) protein antigen are reduced in mutants, but immunized mice challenged secondarily with HEL_46-61 peptide show similar response to wild-type mice

increased immature B cell number
- higher percentages of immature B cells lacking surface IgD and CD23 expression

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv * C57BL * C57BL/10 * C57BR

cellular phenotype

abnormal T cell proliferation
- proliferative responses to intact protein antigens are reduced in mutants, but immunized mice challenged secondarily with OVA_323-339 peptide show similar response to wild-type mice

hematopoietic system phenotype

abnormal B cell differentiation
- B cell maturation is defective

abnormal T cell proliferation
- proliferative responses to intact protein antigens are reduced in mutants, but immunized mice challenged secondarily with OVA_323-339 peptide show similar response to wild-type mice

increased immature B cell number
- higher percentages of immature B cells lacking surface IgD and CD23 expression

immune system phenotype

abnormal antigen presentation via MHC class II
- spleen cells from mice with an H-2^k haplotype background effectively function as stimulators for allogeneic T cells, eliciting strong mixed lymphocyte responses

abnormal B cell differentiation
- B cell maturation is defective

abnormal dendritic cell antigen presentation
- dendritic cells show reduced class II surface expression in overnight culture compared to wild-type

abnormal T cell proliferation
- proliferative responses to intact protein antigens are reduced in mutants, but immunized mice challenged secondarily with OVA_323-339 peptide show similar response to wild-type mice

increased immature B cell number
- higher percentages of immature B cells lacking surface IgD and CD23 expression

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv

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

immune 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

mammalian phenotype

hematopoietic system phenotype
- Normal - no evidence for anemia or thrombocytopenia

Genotype: Cd74^tm1Liz/Cd74⁺
involves: 129S/SvEv

mammalian phenotype

hematopoietic system phenotype
- Normal - no evidence for anemia or thrombocytopenia

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
B6.129S-Cd74/J

hematopoietic system phenotype

decreased B cell number
- in the spleen and lymph node

immune system phenotype

decreased B cell number
- in the spleen and lymph node

References

Bikoff EK; Germain RN; Robertson EJ. 1995. Allelic differences affecting invariant chain dependency of MHC class II subunit assembly. Immunity 2(3):301-10PubMed: 7697546 MGI: J:109917

Additional - Cd74^tm1Liz related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Cd74-Alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together. The expected coat color from breeding is albino.
- Additional Breeding and Husbandry Support
Appearance
- albino
  Related Genotype: A/A Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c
Citation
When using the CD74- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002730 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
	Homozygous for Cd74<tm1Liz>, 1 pair minimum

Related Products and Services

Frozen Mouse Embryo	CAn.129S(B6)-Cd74<tm1Liz>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	CAn.129S(B6)-Cd74<tm1Liz>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	CAn.129S(B6)-Cd74<tm1Liz>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	CAn.129S(B6)-Cd74<tm1Liz>/J Frozen Embryos	$3373.50

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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.

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Also Known As:CD74-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Approximate Controls

Additional Information

Selected References

Cd74tm1Liz

Allele Symbol: Cd74tm1Liz

Disease Terms

Research Areas By Phenotype

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

Genotype: Cd74tm1Liz related

Mammalian Phenotype Terms by Genotype

Genotype: Cd74tm1Liz/Cd74tm1Lizinvolves: 129S/SvEv * C57BL/6J

cellular phenotype

growth/size/body region phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Cd74tm1Liz/Cd74tm1LizB6.129S-Cd74

cellular phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Cd74tm1Liz/Cd74tm1Lizinvolves: 129S/SvEv * C57BL/6

immune system phenotype

Genotype: Cd74tm1Liz/Cd74tm1Lizinvolves: 129S/SvEv * BALB/cAn

hematopoietic system phenotype

immune system phenotype

Genotype: Cd74tm1Liz/Cd74tm1Lizinvolves: 129S/SvEv * BALB/c * C57BL

cellular phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Cd74tm1Liz/Cd74tm1Lizinvolves: 129S/SvEv * C57BL * C57BL/10 * C57BR

cellular phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Cd74tm1Liz/Cd74tm1Lizinvolves: 129S/SvEv

hematopoietic system phenotype

immune system phenotype

mammalian phenotype

Genotype: Cd74tm1Liz/Cd74+involves: 129S/SvEv

mammalian phenotype

Genotype: Cd74tm1Liz/Cd74tm1LizB6.129S-Cd74/J

hematopoietic system phenotype

immune system phenotype

References

Additional - Cd74tm1Liz 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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Cd74^tm1Liz

Allele Symbol: Cd74^tm1Liz

Genotype: Cd74^tm1Liz related

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv * C57BL/6J

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
B6.129S-Cd74

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv * C57BL/6

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv * BALB/cAn

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv * BALB/c * C57BL

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv * C57BL * C57BL/10 * C57BR

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
involves: 129S/SvEv

Genotype: Cd74^tm1Liz/Cd74⁺
involves: 129S/SvEv

Genotype: Cd74^tm1Liz/Cd74^tm1Liz
B6.129S-Cd74/J

Additional - Cd74^tm1Liz related