Overview

Also Known As:double H2K^bD^b knockout

These double H2K^bD^b KO mice carry knockout alleles of the MHC class I genes and exhibit decreased susceptibility to viral infection, as well as enhanced motor learning. They are suitable for use in applications related to the study of adaptive immunity, cytoxic T cell response and cerebellar synaptic plasticity.

Donating Investigator

Derry Roopenian, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

H2-K1^tm1Bpe

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	H2-K1	histocompatibility 2, K1, K region

H2-D1^tm1Bpe

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	H2-D1	histocompatibility 2, D region locus 1

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Neurobiology 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 H-2 K^bD^b knock-out mice carry knock-out alleles of the MHC class I genes (K^b null and D^b null) and lack CD8+ TCRalpha/beta T-cells, but have more CD4-positive, alpha beta T cells, and fewer single positive CD8 peripheral T-cells. Mice homozygous for both alleles exhibit diminished innate immune response, have decreased susceptibility to Lymphocytic Choriomeningitis Virus infection, and have an increased cytoxic T cell response to Listeria monocytogenes infection.
These mutant mice exhibit enhanced motor learning, with lowered threshold for induction of long-term depression at parallel fiber- Purkinje cell synapses.

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 H2-K1^tm1Bpe knockout allele (K^b null) and H2-D1^tm1Bpe knockout allele (D^b null) were both created by Dr. Beatrice Perarnau (Institut Pasteur, Paris France).

The K^b null allele has a hypoxanthine phosphoribosyl transferase (HPRT) minigene in the opposite transcriptional orientation replacing the second and third exons (which encode the α1-α2 peptide-presenting domains) of the H2-K^b locus (H2-K1) on chromosome 17. The construct was electroporated into 129P2/OlaHsd-Hprt^b-m3-derived E14TG2a embryonic stem (ES) cells. Mutant animals were outcrossed to C57BL/6J. K^b null animals on a mixed B6;129 genetic background were used as described below.

The D^b null allele has a lacZ gene and a neomycin resistance gene replacing the first three exons of the H2-D^b locus (H2-D1) on chromosome 17. The construct was electroporated into 129P2/OlaHsd-derived CGR-8 embryonic ES cells. Mutant animals were outcrossed to C57BL/6J. The D^b null animals on a mixed B6;129 genetic background were bred to B6;129-K^b null mice to generate the B6;129-D^b K^b double knockout line.

Dr. Derry Roopenian obtained double knock-out mice that had been backcrossed to C57BL/6 for 9 generations, and then further backcrossed the mice to N11 on C57BL/6J. The mice were then maintained as double homozygotes before being cryopreserved as sperm. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Vugmeyster Y; Glas R; Perarnau B; Lemonnier FA; Eisen H; Ploegh H. 1998. Major histocompatibility complex (MHC) class I KbDb -/- deficient mice possess functional CD8+ T cells and natural killer cells. Proc Natl Acad Sci U S A 95(21):12492-7PubMed: 9770513 MGI: J:50337

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Genetics

H2-K1^tm1Bpe

Allele Symbol: H2-K1^tm1Bpe

Allele Name	targeted mutation 1, Beatrice Perarnau
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	H2-K^b-; H-2K^o; K^-; K^b-
Gene Symbol and Name	H2-K1, histocompatibility 2, K1, K region
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	17
Molecular Note	The central part of the H2-K gene, including the second and third exons was replaced by a HPRT minigene.

H2-D1^tm1Bpe

Allele Symbol: H2-D1^tm1Bpe

Allele Name	targeted mutation 1, Beatrice Perarnau
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	D^-; D^b-; H-2 D^bo; H-2D^b-; H-2D^b knockout; H-2D^o; HHD
Gene Symbol and Name	H2-D1, histocompatibility 2, D region locus 1
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	17
Molecular Note	Exons 1, 2 and 3 of the b haplotype gene were replaced with plasmid sequences and a neomycin cassette.

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
- Immunodeficiency
  - T cell deficiency
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - T Cell Receptor Deficiency
- Neurobiology Research
Neurobiology Research
- Behavioral and Learning Defects
Virology Research

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-D1^tm1Bpe/H2-D1^tm1Bpe H2-K1^tm1Bpe/H2-K1^tm1Bpe
involves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

enhanced coordination
- performance in rotarod tests is significantly better than controls on the third day of testing
- testing repeated after 2 weeks of rest and then after another 4 months of rest indicate much better task retention than for controls

mammalian phenotype

nervous system phenotype
- Normal - normal gross cerebellar development

mortality/aging

decreased susceptibility to Riboviria infection induced morbidity/mortality
- survive infection with Lymphocytic Choriomeningitis Virus

decreased susceptibility to viral infection induced morbidity/mortality
- survive infection with Lymphocytic Choriomeningitis Virus

nervous system phenotype

increased synaptic depression
- lower threshold for induction if climbing fibers are involved in induction

abnormal glutamate-mediated receptor currents
- increased glutamate transients in climbing fiber synaptic clefts

enhanced paired-pulse facilitation
- significantly increased second excitatory postsynaptic current
- larger paired pulse ratio when paired stimuli are applied to climbing fibers are separated by 50-100 msec

hematopoietic system phenotype

increased CD4-positive, alpha beta T cell number
- numbers increase in parallel to decrease in CD8+ cells

absent CD8-positive, alpha-beta T cells
- CD8+ TCRalpha/beta T-cells not present

decreased CD8-positive, alpha-beta T cell number
- 90% reduction of single positive CD8 peripheral T-cells

immune system phenotype

decreased susceptibility to Riboviria infection induced morbidity/mortality
- survive infection with Lymphocytic Choriomeningitis Virus

decreased susceptibility to viral infection induced morbidity/mortality
- survive infection with Lymphocytic Choriomeningitis Virus

decreased CD8-positive, alpha-beta T cell number
- 90% reduction of single positive CD8 peripheral T-cells

absent CD8-positive, alpha-beta T cells
- CD8+ TCRalpha/beta T-cells not present

increased CD4-positive, alpha beta T cell number
- numbers increase in parallel to decrease in CD8+ cells

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

Genotype: H2-D1^tm1Bpe/H2-D1^tm1Bpe H2-K1^tm1Bpe/H2-K1^tm1Bpe
B6.129P-H2-D1 H2-K1

hematopoietic system phenotype

abnormal cytotoxic T cell physiology
- number of H2-M3/LemA-specific CD8+ T cells is drastically increased compared to wild-type during primary LM infection
- in infected mutants, an enhanced H2-M3/LemA-specific response compared to wild-type is detected after injection of B6 splenocytes pulsed with this peptide

immune system phenotype

abnormal cytotoxic T cell physiology
- in infected mutants, an enhanced H2-M3/LemA-specific response compared to wild-type is detected after injection of B6 splenocytes pulsed with this peptide
- number of H2-M3/LemA-specific CD8+ T cells is drastically increased compared to wild-type during primary LM infection

References

Vugmeyster Y; Glas R; Perarnau B; Lemonnier FA; Eisen H; Ploegh H. 1998. Major histocompatibility complex (MHC) class I KbDb -/- deficient mice possess functional CD8+ T cells and natural killer cells. Proc Natl Acad Sci U S A 95(21):12492-7PubMed: 9770513 MGI: J:50337

Additional - H2-D1^tm1Bpe related

Additional - H2-K1^tm1Bpe related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:H2-D1 Alternate3
- Standard PCR:H2-K1alternate2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as double homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the double H2K^bD^b knockout mouse strain in a publication, please cite the originating article(s) and include JAX stock #019995 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
> >	Heterzygous for H2-K1<tm1Bpe> and Heterozygous for H2-D1<tm1Bpe>

Related Products and Services

Frozen Mouse Embryo	B6.129P2-H2-K1<tm1Bpe> H2-D1<tm1Bpe>/DcrJ Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2-H2-K1<tm1Bpe> H2-D1<tm1Bpe>/DcrJ Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2-H2-K1<tm1Bpe> H2-D1<tm1Bpe>/DcrJ Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129P2-H2-K1<tm1Bpe> H2-D1<tm1Bpe>/DcrJ Frozen Embryo	$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:double H2KbDb knockout

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

H2-K1tm1Bpe

Allele Symbol: H2-K1tm1Bpe

H2-D1tm1Bpe

Allele Symbol: H2-D1tm1Bpe

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: H2-D1tm1Bpe/H2-D1tm1Bpe H2-K1tm1Bpe/H2-K1tm1Bpeinvolves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: H2-D1tm1Bpe/H2-D1tm1Bpe H2-K1tm1Bpe/H2-K1tm1BpeB6.129P-H2-D1 H2-K1

hematopoietic system phenotype

immune system phenotype

References

Additional - H2-D1tm1Bpe related

Additional - H2-K1tm1Bpe 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

Also Known As:double H2K^bD^b knockout

H2-K1^tm1Bpe

Allele Symbol: H2-K1^tm1Bpe

H2-D1^tm1Bpe

Allele Symbol: H2-D1^tm1Bpe

Genotype: H2-D1^tm1Bpe/H2-D1^tm1Bpe H2-K1^tm1Bpe/H2-K1^tm1Bpe
involves: 129P2/OlaHsd * C57BL/6

Genotype: H2-D1^tm1Bpe/H2-D1^tm1Bpe H2-K1^tm1Bpe/H2-K1^tm1Bpe
B6.129P-H2-D1 H2-K1

Additional - H2-D1^tm1Bpe related

Additional - H2-K1^tm1Bpe related