Allele Symbol: Irak4m1Btlr
Name: mutation 1, Bruce Beutler
Alteration at locus: Chemically Induced
Allele Symbol: Ticam1Lps2
Name: lipopolysaccharide 2
Alteration at locus: Chemically Induced
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.
ES Cell Line: Not applicable
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.
Founder genetic background: 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:
Donor: Bruce Beutler, M.D., The Scripps Research Institute
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 email@example.com.
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
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Fee/unit (US $)
|Litter||Recovered litter1; additional fees for any special requests.|
|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.
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