Overview

Also Known As: AHNAK KO

Mice homozygous for this knock-out mutation exhibit decreased T cell proliferation and increased susceptibility to parasitic infection.

Donating Investigator

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

Genetic overview

Genetic Background	Generation

Ahnak^tm1Vtm

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ahnak	AHNAK nucleoprotein (desmoyokin)

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Research Applications

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 this targeted mutation are viable and fertile and do not display any gross physical or behavioral abnormalities. Immunoblot analysis of heart ventricle RNA confirms the absence of expression. Defects in T cell activation and proliferation have been noted. This strain may also be useful in studies of cardiomyocyte physiology.

This allele involves many repeated sequences, making PCR distinction of homozygous and heterozygous genotypes impractical. Southern blot is recommended by the donating lab.

Development

A targeting vector was designed to replace a 5.3-kb genomic fragment containing a segment of the coding region, putative promoter and 5' UTR with a loxP-flanked neomycin resistance gene expression cassette. The targeting vector was linearized and electroporated into 129S1/Sv-p⁺ Tyr⁺ Kitl⁺-derived W9.5 embryonic stem (ES) cells. Clones resistant to G418 and gancyclovir were selected, and homologous recombination was confirmed by Southern blotting. Clones containing the targeted mutation were injected into C57BL/6 blastocysts. Resulting male chimeric mice were bred to C57BL/6 females to obtain heterozygous mice. Heterozygotes were intercrossed to generate homozygotes. This line has been backcrossed to C57BL/6 ten times by the donating laboratory.

Selected References

Komuro A; Masuda Y; Kobayashi K; Babbitt R; Gunel M; Flavell RA; Marchesi VT. 2004. The AHNAKs are a class of giant propeller-like proteins that associate with calcium channel proteins of cardiomyocytes and other cells. Proc Natl Acad Sci U S A 101(12):4053-8PubMed: 15007166 MGI: J:89231

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Genetics

Ahnak^tm1Vtm

Allele Symbol: Ahnak^tm1Vtm

Allele Name	targeted mutation 1, Vincent T Marchesi
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Ahnak^tm1Vtm; targeted mutation 1, Vincent T Marchesi
Gene Symbol and Name	Ahnak, AHNAK nucleoprotein (desmoyokin)
Gene Synonym(s)	AHNAK 1; 2310047C17Rik; UV118; AHNAKRS; RGD1308572; 1110004P15Rik; AA589382; RIKEN cDNA 2310047C17 gene; 2310047C17Rik; AV091586; DY6; RIKEN cDNA 1110004P15 gene; expressed sequence AV091586; expressed sequence AA589382; 1110004P15Rik; PM227
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	19
Molecular Note	A floxed neo cassette replaced 5.3 kb of sequence encompassing the putative promoter, 5' UTR, and a segment of the coding region. Northern blot of mutant heart ventricles indicated no transcript was present, and absence of normal protein was confirmed by immunoblot.
Mutations Made By	Vincent Marchesi, Yale University

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - T cell deficiency

Mammalian Phenotype Terms by Genotype

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

Genotype: Ahnak^tm1Vtm/Ahnak^tm1Vtm
involves: 129S1/Sv * C57BL/6

cellular phenotype

decreased T cell proliferation
- Normal - addition of ionomycin also rescues the proliferation defect
- CD 4 T cells stimulated with anti-CD3 antibody proliferate poorly with only 23% of cells undergoing cell division compared to 40% of wild-type controls
- Normal - exogenous administration of IL-2 rescues the proliferation defect

hematopoietic system phenotype

abnormal T cell activation
- calcium influx of stimulated CD4 T cells is markedly reduced

abnormal T-helper 1 physiology
- mice do not mount an effective Th1 response to L. major footpad infection as measured by decreased production of IFN-gamma by CD4 T cells

decreased T cell proliferation
- Normal - addition of ionomycin also rescues the proliferation defect
- CD 4 T cells stimulated with anti-CD3 antibody proliferate poorly with only 23% of cells undergoing cell division compared to 40% of wild-type controls
- Normal - exogenous administration of IL-2 rescues the proliferation defect

immune system phenotype

abnormal T cell activation
- calcium influx of stimulated CD4 T cells is markedly reduced

abnormal T-helper 1 physiology
- mice do not mount an effective Th1 response to L. major footpad infection as measured by decreased production of IFN-gamma by CD4 T cells

decreased interferon-gamma secretion
- popliteal CD4 T cells from L. major infected mice secrete up to 10-fold less IFN-gamma than wild-type controls

decreased interleukin-2 secretion
- CD 4 T cells stimulated with anti-CD3 antibody for one or two days produce little IL-2

decreased T cell proliferation
- Normal - addition of ionomycin also rescues the proliferation defect
- CD 4 T cells stimulated with anti-CD3 antibody proliferate poorly with only 23% of cells undergoing cell division compared to 40% of wild-type controls
- Normal - exogenous administration of IL-2 rescues the proliferation defect

increased interleukin-4 secretion
- popliteal CD4 T cells from L. major infected mice secrete more IL-4 than wild-type controls

increased susceptibility to parasitic infection
- mice exhibit enhanced lesion development and a 100-fold increase in parasite burden after infection with L. major in the footpad

References

Komuro A; Masuda Y; Kobayashi K; Babbitt R; Gunel M; Flavell RA; Marchesi VT. 2004. The AHNAKs are a class of giant propeller-like proteins that associate with calcium channel proteins of cardiomyocytes and other cells. Proc Natl Acad Sci U S A 101(12):4053-8PubMed: 15007166 MGI: J:89231

Additional - Ahnak^tm1Vtm related

Technical Support

Contact Technical Support

Genotyping Protocols
- Probe: Generic Neo
- Genotyping resources and troubleshooting
Breeding Considerations

When maintained as a live colony, homozygous crosses may be used.
- Additional Breeding and Husbandry Support
Citation
When using the AHNAK KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #007011 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	Genotype	Price
	Heterozygous or wildtype for Ahnak<tm1Vtm>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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Frozen Mouse Embryo

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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.

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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.

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Licensing Information

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Also Known As: AHNAK KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Ahnaktm1Vtm

Allele Symbol: Ahnaktm1Vtm

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ahnaktm1Vtm/Ahnaktm1Vtminvolves: 129S1/Sv * C57BL/6

cellular phenotype

hematopoietic system phenotype

immune system phenotype

References

Additional - Ahnaktm1Vtm 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

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Ahnak^tm1Vtm

Allele Symbol: Ahnak^tm1Vtm

Genotype: Ahnak^tm1Vtm/Ahnak^tm1Vtm
involves: 129S1/Sv * C57BL/6

Additional - Ahnak^tm1Vtm related