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Strain Name:
C57BL/6J-Irak4m1Btlr Ticam1Lps2/Mmucd
Stock Number:
030625-UCD
Citation ID:
RRID:MMRRC_030625-UCD
Other Names:
otiose/Lps2 double mutant, C57BL/6J-Irak4m1Btlr Ticam1Lps2/Mmcd
Major Collection:

Strain Information

Irak4m1Btlr
Name: interleukin-1 receptor-associated kinase 4; mutation 1, Bruce Beutler
Synonyms: otiose
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 15
Alteration at locus: Chemically Induced
Ticam1Lps2
Name: TIR domain containing adaptor molecule 1; lipopolysaccharide 2
Synonyms: Trifm, Ticam1M1Btlr, Ticam1-, Lps, TRIF-, TrifLps2, Lps2, Lps2-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 15
Alteration at locus: Chemically Induced
Irak4
Name: interleukin-1 receptor-associated kinase 4
Synonyms: NY-REN-64, IRAK-4, 9330209D03Rik, 8430405M07Rik
Type: Gene
Species: Mouse
Chromosome: 15
Alteration at locus: Chemically Induced
NCBI: 266632
Homologene: 41109
Ticam1
Name: TIR domain containing adaptor molecule 1
Synonyms: Trif, TICAM-1
Type: Gene
Species: Mouse
Chromosome: 17
Alteration at locus: Chemically Induced
NCBI: 106759
Homologene: 8605
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
Phenotype
Homozygous: 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:
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.
Mammalian Phenotype Terms
Allelic Composition: Irak4m1Btlr/Irak4m1Btlr (Genetic Background: C57BL/6J-Irak4m1Btlr )

  • immune system
    • decreased tumor necrosis factor secretion [MP:0008561]
Allelic Composition: Ticam1Lps2/Ticam1Lps2 (Genetic Background: C57BL/6J-Ticam1Lps2 )

Allelic Composition: Ticam1Lps2/Ticam1Lps2 (Genetic Background: C57BL/6J-Ticam1Lps2/J )

Allelic Composition: Ticam1Lps2/Ticam1Lps2 (Genetic Background: involves: C57BL/6 )

MeSH Terms
  • Alleles
  • Animals
  • Autoimmune Diseases/genetics
  • Autoimmune Diseases/immunology
  • Autoimmune Diseases/microbiology
  • Autoimmunity/genetics
  • Ethylnitrosourea/pharmacology
  • Homozygote
  • Inflammation/genetics
  • Inflammation/immunology
  • Inflammation/microbiology
  • Interleukin-1/genetics
  • Interleukin-1/immunology
  • Interleukin-1 Receptor-Associated Kinases/genetics
  • Interleukin-1 Receptor-Associated Kinases/immunology
  • Listeriosis/immunology
  • Mice
  • Mice, Mutant Strains
  • Mutagenesis
  • Mutation
  • Myeloid Differentiation Factor 88/genetics
  • Myeloid Differentiation Factor 88/immunology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics
  • Receptors, Interleukin-1/immunology
  • Toll-Like Receptors/immunology
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

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@ucdavis.edu. Older strains may not have this information.
  • Immunology and Inflammation
  • Models for Human Disease
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

Colony Surveillance Program and Current Health Reports

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

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

Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

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.

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 $)
*Shipping & Handling not included*
Units Notes
030625-UCD-EMBRYO Cryo-preserved embryos $1,038.00 / Non-Profit Aliquot Approximate quantity2 : 20-40 embryos / aliquot
030625-UCD-SPERM Cryo-preserved spermatozoa $546.25 / Non-Profit Aliquot Approximate quantity3
030625-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.

1 The distribution fee covers the expense of rederiving mice from a live mouse; 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 contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 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.

4 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.

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.