Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   20-JUN-12 Species laboratory mouse Generation N11+F4 (16-APR-13) Generation Definitions   Donating Investigator Dr. David Russell,   Univ of Texas Southwest Med Ctr Dallas

Description
Stimulation of toll-like receptors has been shown to normally induce the expression of Ch25h (cholesterol 25-hydroxylase) in macrophages. Il2 (interleukin 2)-mediated stimulation of B cell proliferation is suppressed, activation-induced cytidine deaminase (AID) expression is repressed, and immunoglobulin class switch recombination is blocked, leading to markedly decreased IgA production.

The Ch25h gene was deleted in this targeted mutant strain. Homozygotes have excessive levels of IgA in their sera, mucosa, and the bronchial fluid of the lungs. This strain may be useful in studies of innate immune system regulation of adaptive immune responses.

Development
The intron-less gene was deleted in its entirety and replaced by the PolII neo pA expression cassette in 129S6/SvEvTac-derived SM1 embryonic stem (ES) cells. This strain was backcrossed to C57BL/6J for more than 10 generations by the donating laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Ch25h^tm1Rus/Ch25h^tm1Rus

        B6.129S6-Ch25h^tm1Rus

• immune system phenotype
• increased IgA level
  • in the sera, lungs, and intestinal mucosa   (MGI Ref ID J:170807)
• increased IgG2a level
  • in the sera, lungs, and intestinal mucosa   (MGI Ref ID J:170807)
• increased IgG2b level
  • in the intestinal mucosa   (MGI Ref ID J:170807)
• increased IgG3 level
  • in the intestinal mucosa   (MGI Ref ID J:170807)

View Research Applications

Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      B cell defects
      Macrophage defects
      defects in humoral immune responses

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ch25htm1Rus
Allele Name		targeted mutation 1, David W Russell
Allele Type		Targeted (knock-out)
Strain of Origin		129S6/SvEvTac
Gene Symbol and Name		Ch25h, cholesterol 25-hydroxylase
Chromosome		19
Gene Common Name(s)		AI462618; C25H; expressed sequence AI462618; m25OH;
Molecular Note		The intron-less gene was deleted in its entirety and replaced by the PolII neo pA expression cassette. The absence of protein expression was confirmed by western blot analysis on lung and liver extracts after Kdo2-Lipid A induction. [MGI Ref ID J:170807]

Genotyping

Genotyping Information

Genotyping Protocols

Ch25h^tm1Rus, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Bauman DR; Bitmansour AD; McDonald JG; Thompson BM; Liang G; Russell DW. 2009. 25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production. Proc Natl Acad Sci U S A 106(39):16764-9. [PubMed: 19805370]  [MGI Ref ID J:170807]

Additional References

Ch25h^tm1Rus related

Hannedouche S; Zhang J; Yi T; Shen W; Nguyen D; Pereira JP; Guerini D; Baumgarten BU; Roggo S; Wen B; Knochenmuss R; Noel S; Gessier F; Kelly LM; Vanek M; Laurent S; Preuss I; Miault C; Christen I; Karuna R; Li W; Koo DI; Suply T; Schmedt C; Peters EC; Falchetto R; Katopodis A; Spanka C; Roy MO; Detheux M; Chen YA; Schultz PG; Cho CY; Seuwen K; Cyster JG; Sailer AW. 2011. Oxysterols direct immune cell migration via EBI2. Nature 475(7357):524-7. [PubMed: 21796212]  [MGI Ref ID J:174682]

Liu SY; Aliyari R; Chikere K; Li G; Marsden MD; Smith JK; Pernet O; Guo H; Nusbaum R; Zack JA; Freiberg AN; Su L; Lee B; Cheng G. 2013. Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity 38(1):92-105. [PubMed: 23273844]  [MGI Ref ID J:193039]

Yi T; Wang X; Kelly LM; An J; Xu Y; Sailer AW; Gustafsson JA; Russell DW; Cyster JG. 2012. Oxysterol Gradient Generation by Lymphoid Stromal Cells Guides Activated B Cell Movement during Humoral Responses. Immunity 37(3):535-48. [PubMed: 22999953]  [MGI Ref ID J:188276]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Mating System	Homozygote x Homozygote         (Female x Male)   20-JUN-12

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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'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.

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