Overview

Also Known As:B2m KO

Mice homozygous for the B2m^tm1Unc targeted mutation have little if any MHC class I protein expression on the cell surface. There are few CD8⁺ cytotoxic T-cells and under some circumstances a compensatory increase in CD4⁺ cytotoxic T-cells. Immune responses involving CD8⁺ T-cells are severely deficient, providing a model to assess the role of CD8⁺ cells and class I MHC in various experimental systems.

Donating Investigator

Dr. Oliver Smithies, University of North Carolina at Chapel Hill

Beverly H Koller, University of North Carolina at Chapel Hill

Genetic overview

Genetic Background	Generation
	Contact Technical Support (2019-05-14 00:00:00)

B2m^tm1Unc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	B2m	beta-2 microglobulin

View Genetics

Research Applications

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

View All Research Applications

Base Price

Starting at:

$125.99 Domestic price for male 3-week

View Price List

Details

Detailed Description

Mice homozygous for the B2m^tm1Unc targeted mutation have little if any MHC class I protein expression on the cell surface. There are few CD8⁺ cytotoxic T-cells and under some circumstances a compensatory increase in CD4⁺ cytotoxic T-cells. Immune responses involving CD8⁺ T-cells are severely deficient providing a model to assess the role of CD8⁺ cells and class I MHC in various experimental systems. Hemachromatosis has been noted in certain genetic backgrounds (Rothenberg BE, Voland JR, Proc Natl Acad Sci USA 93:1529-34, 1996).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

The B2m^tm1Unc mutant strain was developed in the laboratory of Dr. Beverly Koller and Dr. Oliver Smithies at the University of North Carolina at Chapel Hill. It was generated by a targeted disruption of the B2m gene. The 129-derived E14TG2a ES cell line was used. The C57BL/6J strain was produced by backcrossing the B2m^tm1Unc mutation 11 times to C57BL/6J inbred mice in the laboratory of Dr. Derry Roopenian at The Jackson Laboratory.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Koller BH; Marrack P; Kappler JW; Smithies O. 1990. Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science 248(4960):1227-30PubMed: 2112266 MGI: J:64451

View All References

Genetics

B2m^tm1Unc

Allele Symbol: B2m^tm1Unc

Allele Name	targeted mutation 1, University of North Carolina
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	b2m^null; beta2M-; beta2m⁰; beta2m^null; beta2m^o; beta2m^tm1Unc; beta2MKO; beta2-m-KO; I⁰; MHC-I^-
Gene Symbol and Name	B2m, beta-2 microglobulin
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	2
Molecular Note	Insertion of a neomycin-resistance gene into the second exon.
Mutations Made By	Dr. Oliver Smithies, University of North Carolina at Chapel Hill

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: B2m^tm1Unc related

Hematological Research
- Anemia, Iron Deficiency and Transport Defects
  - hemochromatosis
Internal/Organ Research
- Liver Defects
  - hemochromatosis
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - MHC class I deficiency
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - MHC class I deficiency
Metabolism Research
- Hemochromatosis
  - iron metabolism 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: B2m^tm1Unc/B2m^tm1Unc
involves: 129P2/OlaHsd * C57BL/6

hematopoietic system phenotype

abnormal T cell number
- mucosal-associated invariant T cells (MAIT) that express the canonical mVa19-Ja33 TCR rearrangement and are typically found in the gut lamina propia are virtually absent in these mice
- when these mice serve as bone marrow donors, MAIT T cells are absent in the gut of irradiated hosts
- when wild-type bone marrow is transferred into these mice, MAIT T cells are found in the gut

absent CD8-positive, alpha-beta T cells
- CD8+CD4- T cells from the thymus of five week old mice are almost non-existent in comparison to control (0.8% vs. 6.7%), however, total numbers of alpha beta T cells and CD8-CD4+ T cells do not differ significantly from control
- deficient in CD4-CD8+ T cells

immune system phenotype

abnormal T cell number
- when these mice serve as bone marrow donors, MAIT T cells are absent in the gut of irradiated hosts
- mucosal-associated invariant T cells (MAIT) that express the canonical mVa19-Ja33 TCR rearrangement and are typically found in the gut lamina propia are virtually absent in these mice
- when wild-type bone marrow is transferred into these mice, MAIT T cells are found in the gut

absent CD8-positive, alpha-beta T cells
- CD8+CD4- T cells from the thymus of five week old mice are almost non-existent in comparison to control (0.8% vs. 6.7%), however, total numbers of alpha beta T cells and CD8-CD4+ T cells do not differ significantly from control
- deficient in CD4-CD8+ T cells

decreased level of surface class I molecules
- surface expression of class I molecules in cells from lymph nodes, spleen and thymus cannot be detected by flow cytometry

Genotype: B2m^tm1Unc/B2m⁺
involves: 129P2/OlaHsd * C57BL/6

hematopoietic system phenotype

decreased CD8-positive, alpha-beta T cell number
- numbers of CD8+CD4- T cells from the thymus of five week old mice are reduced in comparison to control (4.9% vs. 6.7%), however, in peripheral lymphoid tissues numbers of CD8+CD4- T cells do not differ from control

immune system phenotype

decreased CD8-positive, alpha-beta T cell number
- numbers of CD8+CD4- T cells from the thymus of five week old mice are reduced in comparison to control (4.9% vs. 6.7%), however, in peripheral lymphoid tissues numbers of CD8+CD4- T cells do not differ from control

decreased level of surface class I molecules
- surface expression of class I molecules in cells from lymph nodes are reduced in comparison to control

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

Genotype: B2m^tm1Unc/B2m^tm1Unc
B6.129P2-B2m/DcrJ

endocrine/exocrine gland phenotype

abnormal pancreas morphology
- mice develop peri-islet T cell aggregates >30 weeks of age

immune system phenotype

increased susceptibility to infection induced morbidity/mortality
- following infection with either a low or high dose of IOE, 90% of mice survive a low dose and all mice succumb to a high dose

decreased susceptibility to bacterial infection
- mice are highly resistant to infection with a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE) following infection with either a low or high dose of IOE, 90% of mice survive a low dose with mild illness and all mice succumb to a high dose
- at day 12 and 14 post-infection with a lethal low dose of IEO, mice exhibit only mild liver pathology, few apoptotic foci in the liver and preserved lymphoid tissue cellularity
- following infection with IEO, CD8+ T cells in the spleen are reduced (1.5%+/-0.1% of splenocytes compared to 9.7%+/-0.7% of splenocytes in wild-type mice)
- to a high dose
- mice have lower burdens of Ehrlichia bacteria in the lungs and spleen following infection than do wild-type mice

decreased susceptibility to autoimmune diabetes
- when splenocytes from diabetic donors are transferred into lethally-irradiated 8-week old recipients, female mice remain normoglycemic for about 17 weeks before developing hyperglycemia/diabetes; kinetics are much slower than in B2m-null, Tg(GFAP-B2m)Mdos (line 9 or 14) transgenic mice
- (line 9 or 14) transgenic mice
- mice do not develop spontaneous diabetes compared to wild-type NOD controls

decreased CD8-positive, alpha-beta T cell number
- in uninfected mice the number of CD8+ T cells in the spleen is reduced compared to in wild-type mice
- following infection with a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), CD8+ T cells in the spleen are reduced (1.5%+/-0.1% of splenocytes compared to 9.7%+/-0.7% of splenocytes in wild-type mice)

decreased IgG level

abnormal interleukin level
- following infection with a lethal low dose of a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), induces less IL-10 than in infected wild-type mice

increased T-helper 1 cell number
- following infection with a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), the number of interferon-gamma producing CD4+ Th1 cells in the spleen on day 8 and day 12 is increased relative to in infected wild-type mice

abnormal tumor necrosis factor level
- following infection with a lethal low dose of a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), induces less TNF-alpha than in infected wild-type mice

increased IgM level

mortality/aging

increased susceptibility to infection induced morbidity/mortality
- following infection with either a low or high dose of IOE, 90% of mice survive a low dose and all mice succumb to a high dose

hematopoietic system phenotype

decreased CD8-positive, alpha-beta T cell number
- in uninfected mice the number of CD8+ T cells in the spleen is reduced compared to in wild-type mice
- following infection with a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), CD8+ T cells in the spleen are reduced (1.5%+/-0.1% of splenocytes compared to 9.7%+/-0.7% of splenocytes in wild-type mice)

increased IgM level

decreased IgG level

increased T-helper 1 cell number
- following infection with a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), the number of interferon-gamma producing CD4+ Th1 cells in the spleen on day 8 and day 12 is increased relative to in infected wild-type mice

homeostasis/metabolism phenotype

abnormal interleukin level
- following infection with a lethal low dose of a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), induces less IL-10 than in infected wild-type mice

decreased circulating serum albumin level

abnormal tumor necrosis factor level
- following infection with a lethal low dose of a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), induces less TNF-alpha than in infected wild-type mice

References

Koller BH; Marrack P; Kappler JW; Smithies O. 1990. Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science 248(4960):1227-30PubMed: 2112266 MGI: J:64451

Additional References

Arnett HA; Wang Y; Matsushima GK; Suzuki K; Ting JP. 2003. Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration. J Neurosci 23(30):9824-32PubMed: 14586011 MGI: J:88200
Capone M; Lees RK; Finke D; Ernst B; Meerwijk JP; MacDonald HR. 2003. Selective absence of CD8+ TCRalpha beta+ intestinal epithelial cells in transgenic mice expressing beta2-microglobulin-associated ligands exclusively on thymic cortical epithelium. Eur J Immunol 33(6):1471-7PubMed: 12778464 MGI: J:83888
Chiang EY; Stroynowski I. 2004. A nonclassical MHC class I molecule restricts CTL-mediated rejection of a syngeneic melanoma tumor. J Immunol 173(7):4394-401PubMed: 15383569 MGI: J:93729
Dao T; Exley M; Mehal WZ; Tahir SM; Snapper S; Taniguchi M; Balk SP; Crispe IN. 2001. Involvement of CD1 in peripheral deletion of T lymphocytes is independent of NK T cells. J Immunol 166(5):3090-7PubMed: 11207260 MGI: J:76978
Hayashi K; Abe N; Watanabe T; Obinata M; Ito M; Sato T; Habu S; Satake M. 2001. Overexpression of AML1 transcription factor drives thymocytes into the CD8 single-positive lineage. J Immunol 167(9):4957-65PubMed: 11673502 MGI: J:72699
Jude BA; Pobezinskaya Y; Bishop J; Parke S; Medzhitov RM; Chervonsky AV; Golovkina TV. 2003. Subversion of the innate immune system by a retrovirus. Nat Immunol 4(6):573-8PubMed: 12730691 MGI: J:83088
Konishi J; Iwabuchi K; Iwabuchi C; Ato M; Nagata JI; Onoe K; Nakagawa KI; Kasai M; Ogasawara K; Kawakami K; Onoe K. 2000. Thymic epithelial cells responsible for impaired generation of NK-T thymocytes in Alymphoplasia mutant mice. Cell Immunol 206(1):26-35PubMed: 11161435 MGI: J:67083
Li L; Sullivan BA; Aldrich CJ; Soloski MJ; Forman J; Grandea AG 3rd; Jensen PE; Van Kaer L. 2004. Differential requirement for tapasin in the presentation of leader- and insulin-derived peptide antigens to Qa-1b-restricted CTLs. J Immunol 173(6):3707-15PubMed: 15356116 MGI: J:92768
Murphy EA; Sathiyaseelan J; Parent MA; Zou B; Baldwin CL. 2001. Interferon-gamma is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice. Immunology 103(4):511-8PubMed: 11529943 MGI: J:71148
Pien GC; Nguyen KB; Malmgaard L; Satoskar AR; Biron CA. 2002. A unique mechanism for innate cytokine promotion of T cell responses to viral infections. J Immunol 169(10):5827-37PubMed: 12421964 MGI: J:80075
Pigeon C; Ilyin G; Courselaud B; Leroyer P; Turlin B; Brissot P; Loreal O. 2001. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 276(11):7811-9PubMed: 11113132 MGI: J:67983
Urdahl KB; Liggitt D; Bevan MJ. 2003. CD8+ T cells accumulate in the lungs of Mycobacterium tuberculosis-infected Kb-/-Db-/- mice, but provide minimal protection. J Immunol 170(4):1987-94PubMed: 12574368 MGI: J:82297

Additional - B2m^tm1Unc related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:B2m
- Standard PCR:B2m
- Genotyping resources and troubleshooting
Breeding Considerations

This strain is a good breeder.

This B2m^tm1Unc strain is maintained by mating homozygous siblings. Only homozygous mice may be ordered. Expected coat color from breeding:Black
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Appearance
- black
  Related Genotype: a/a
Citation
When using the B2m KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002087 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

RB11 (Maximum)

Pricing & Availability

Available Now

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for B2m<tm1Unc>

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:B2m KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

B2mtm1Unc

Allele Symbol: B2mtm1Unc

Disease Terms

Research Areas By Phenotype

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

Genotype: B2mtm1Unc related

Mammalian Phenotype Terms by Genotype

Genotype: B2mtm1Unc/B2mtm1Uncinvolves: 129P2/OlaHsd * C57BL/6

hematopoietic system phenotype

immune system phenotype

Genotype: B2mtm1Unc/B2m+involves: 129P2/OlaHsd * C57BL/6

hematopoietic system phenotype

immune system phenotype

Genotype: B2mtm1Unc/B2mtm1UncB6.129P2-B2m/DcrJ

endocrine/exocrine gland phenotype

immune system phenotype

mortality/aging

hematopoietic system phenotype

homeostasis/metabolism phenotype

References

Additional References

Additional - B2mtm1Unc related

Genotyping Protocols

Breeding Considerations

Mating System

Appearance

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

B2m^tm1Unc

Allele Symbol: B2m^tm1Unc

Genotype: B2m^tm1Unc related

Genotype: B2m^tm1Unc/B2m^tm1Unc
involves: 129P2/OlaHsd * C57BL/6

Genotype: B2m^tm1Unc/B2m⁺
involves: 129P2/OlaHsd * C57BL/6

Genotype: B2m^tm1Unc/B2m^tm1Unc
B6.129P2-B2m/DcrJ

Additional - B2m^tm1Unc related