Strain Detail Sheet

Strain Name    :

C57BL/6J-Irak4m1Btlr Ticam1Lps2/Mmucd

Stock Number :

030625-UCD

Other Names   :

otiose/Lps2 double mutant, C57BL/6J-Irak4m1Btlr Ticam1Lps2/Mmcd

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Irak4m1Btlr
Name: mutation 1, Bruce Beutler
Alteration at locus: Chemically Induced
Allele Symbol: Ticam1Lps2
Name: lipopolysaccharide 2
Alteration at locus: Chemically Induced

Genetic Alterations:
Mice are double mutants for Ticam1 and Irak4. The mutation in Ticam1 corresponds to a single nucleotide deletion of a G at position 2258 (in exon 2 of 2 total exons), causing a frameshift which deletes 24 amino acids from the C- terminus of the protein and replaces them with 11 unrelated amino acids followed by a premature stop (Genbank Accession NM_174989). The mutation in Irak4 corresponds to a T to C transition at position 1094 of the Irak4 gene, in exon 9 of 12 total exons (Genbank: NM_029926). This results in a conversion of isoleucine to threonine at residue 327 of the IRAK-4 protein.

Genotype Determination:

ES Cell Line: Not Applicable

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Homozygous phenotype: Essentially, the otiose (Irak4)/Lps2 (Ticam1 or Trif) double mutant is equivalent to a MyD88/Trif double mutant (IRAK4 is necessary for MyD88 signaling). These are the two major adaptor molecules for Toll-like Receptor (TLR) signaling (some TLR receptors signal through MyD88 only, some through Trif only, some through both). These animals are unresponsive to all TLR signaling, which is critical for the innate immune system. These animals are severely immunocompromised and are highly susceptible to infection by bacteria and viruses such as MCMV.

Heterozygous phenotype: Animals that are heterozygous for Irak4 are normal while animals heterozygous for Lps2 displayed partially defective responses to LPS, lipid A and poly I:C (TLR3 and TLR4 signaling). Signaling via TLRs 1, 2, 6, 7, and 9 are not affected by the Lps2 mutation. The double heterozygous animals are expected to behave like Lps2 heterozygous animals.

Strain of Origin: C57BL/6J

Strain genetic background: C57BL/6J

Strain Development: Both the Lps2 and otiose mutations were generated and maintained on a C57BL/6J background. The otiose/Lps2 double homozygous mutant was generated by crossing the two strains to each other for several generations.

Suggested Control Mice:

  • Wildtype littermates

Research Applications

  • Immunology and Inflammation
  • Models for Human Disease

Strain Origin

Donor: Bruce Beutler, M.D., The Scripps Research Institute

Primary Reference:

  • Croker BA; Lawson BR; Berger M; Eidenschenk C; Blasius AL; Moresco EM; Sovath S; Cengia L; Shultz LD; Theofilopoulos AN; Pettersson S; Beutler BA, Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger., Proc Natl Acad Sci U S A 2008 Sep 30;105(39):15028-33 (Medline PMID: 18806225)
  • Kasper Hoebe, Eva Marie Y. Moresco, Bruce Beutler. Record for “Lps2”, updated December 5th, 2007. MUTAGENETIX (TM), B. Beutler and colleaugues, Department of Genetics, The Scripps Research Institute.)
  • Michael Berger, Eva Marie Y. Moresco, Bruce Beutler. Record for “Otiose”, updated September 24th, 2007. MUTAGENETIX (TM),B. Beutler and colleaugues, Department of Genetics, The Scripps Research Institute.)

Colony and Husbandry Information

Special Considerations

None.

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution [Including applicable technology transfer agreements]

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # - Description Distribution
Fee/unit (US $)
Units Notes
030625-UCD-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
030625-UCD-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2
030625-UCD-EMBRYOCryo-preserved embryos
$1,038.00
Non-Profit
Aliquot Approximate quantity3: 20-40 embryos / aliquot

1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

This site requires JavaScript. Tested for Firefox 3.5+, Microsoft Internet Explorer 7+, Google Chrome.

Generated: 04/23/2014