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Strain Name:

C.C3-Tlr4Lps-d/J

Stock Number:

002930

Availability:

Level 4

Price and Supply Information

General Terms and Conditions

Genes & Alleles   Tlr4;   Tlr4Lps-d;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Background Strain BALB/cAnPt
Donor Strain C3H/HeJ
GenerationN20F55 (11-JAN-08)

Appearance
agouti
Related Genotype: A/A Tyrp1+/Tyrp1+

Strain Description
In addition to the Tlr4Lps-d congenic interval from C3H/HeJ, this strain is also congenic for the wild type tyrosinase allele from C3H/HeJ on chromosome 7. This strain provides a tool for analysis of markers in the region and for examining functional effects of Lpsd on BALB/c, a strain susceptible to infection, neoplastic disease including the induction of plasmacytomas and other tumors.

Strain Development
The Lps-d mutation arose in C3H/HeJ sometime between 1960 and 1968. In 1977 a C3H/HeJ female, derived from the colony of David Sachs at NIH, was crossed with a BALB/cAnPt male and the Tlr4Lps-d allele was transferred onto the BALB/cAnPt background by continued backcrossing. At that time it was thought that Tlr4 and Tyrp1 were tightly linked so the black mice, those that would be carrying the C3H/HeJ-derived dominant B (wild-type) allele of Typr1 rather than being homozygous for the BALB/cAnPt-derived recessive b allele and Tyrc allele, were selected at each generation to continue the backcross. At N6 intercrossing made the strain homozygous for Tlr4Lps-d and Tyrp1B. Backcrossing to BALB/cAnPt was resumed from N6F22. When backcrossing reached N20, the strain was intercrossed to generate this strain homozygous for Tlr4Lps-d and Tyrp1B but not Tyrc. The congenic interval encompassing Tyrp1B and Tlr4Lps-d includes at least from D4Mit151 through D4Mit26. In March 1977, this strain was imported into The Jackson Laboratory from Dr. Stephanie Vogel at Uniformed Services University of the Health Sciences.

Related Disease (OMIM) Terms

Toll-Like Receptor 4; TLR4
Mammalian Phenotype Terms assigned by genotype

Tlr4Lps-d/Tlr4Lps-d

        C.C3-Tlr4Lps-d/J
  • cardiovascular system phenotype
  • decreased response of heart to induced stress (MGI Ref ID J:106358)
    • exhibit reduced cardiac hypertrophy following pressure overload compared to controls
    • exhibit no significant myocardial interstitial fibrosis or cardiac myocyte death following pressure overload unlike wild type

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Tlr4Lps-d/Tlr4Lps-d

        involves: C3H/HeJ
  • immune system phenotype
  • abnormal T-helper 2 physiology (MGI Ref ID J:96356)
    • Th2 responses elevated after induction of autoimmune arthritis
  • increased susceptibility to bacterial infection (MGI Ref ID J:5721)
    • low responsiveness of spleen cells to lipopolysaccharides
    • increased sensitivity to gram (-) infection
    • significantly shortened survival after infection with Klebsiella pneumoniae
    • increased K. pneumoniae levels in the lung
  • susceptibility to induced arthritis (MGI Ref ID J:96356)
    • reduced susceptibility to arthritis induced by type II collagen
  • behavior/neurological phenotype
  • hyporesponsive to tactile stimuli (MGI Ref ID J:97819)
    • reduced mechanical allodynia after nerve injury
  • increased thermal nociceptive threshold (MGI Ref ID J:97819)
    • attenuated response to heat
  • touch/vibrissae phenotype
  • hyporesponsive to tactile stimuli (MGI Ref ID J:97819)
    • reduced mechanical allodynia after nerve injury
  • increased thermal nociceptive threshold (MGI Ref ID J:97819)
    • attenuated response to heat
  • skeleton phenotype
  • susceptibility to induced arthritis (MGI Ref ID J:96356)
    • reduced susceptibility to arthritis induced by type II collagen
  • muscle phenotype
  • *normal* muscle phenotype (MGI Ref ID J:116310)
    • MCP-1 (monocyte chemoattractant protein-1) release from isolated mouse aorta smooth muscle cells (MAoSMC) by stimulation with dsRNA is normal relative to controls

Tlr4Lps-d/Tlr4Lps-d

        C3H/HeJ-Tlr4Lps-d
  • immune system phenotype
  • abnormal phagocyte morphology (MGI Ref ID J:125179)
    • phagocytes fail to respond to LPS stimulation
    • however, response to stimulation with TLR9 or TLR7 and TLR8 with their ligands (CpG and R848, respectively) is similar to in wild type cells
  • liver inflammation (MGI Ref ID J:135830)
    • after BDL, necroinflammatory foci and lymphocytic infiltration are obviously less than in controls
  • hematopoietic system phenotype
  • *normal* hematopoietic system phenotype (MGI Ref ID J:135830)
    • B cell apoptosis in Peyer's patch is not observed after bile duct ligation (BDL)
    • abnormal phagocyte morphology (MGI Ref ID J:125179)
      • phagocytes fail to respond to LPS stimulation
      • however, response to stimulation with TLR9 or TLR7 and TLR8 with their ligands (CpG and R848, respectively) is similar to in wild type cells
  • life span-post-weaning/aging
  • abnormal induced morbidity/mortality (MGI Ref ID J:121930)
    • bacterial lipoteichoic acid exposure after priming by IFNgamma and sensitization with D-galactosamine induces lethal shock in Tlr4-deficient mutants, while Tlr2- and Tlr2/4-doubly deficient mice are protected
    • systemic challenge with Myr3-CSK4 (a synthetic lipopeptide) after D-galactosamine induces lethal shock in wild type mice, but mutants are protected
    • heat-inactivated E. coli exposure results in fatal toxemia as in wild type mice
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype (MGI Ref ID J:135830)
    • after BDL, serum alanine transaminase levels are not different from controls
  • liver/biliary system phenotype
  • abnormal hepatocyte morphology (MGI Ref ID J:135830)
    • confluent foci of feathery hepatocyte degeneration due to bile acid cytotoxicity are significantly reduced compared to controls 24 hours after BDL
    • decreased hepatocyte apoptosis (MGI Ref ID J:135830)
      • hepatocyte cell death is reduced compared to controls after BDL
  • focal hepatic necrosis (MGI Ref ID J:135830)
  • liver inflammation (MGI Ref ID J:135830)
    • after BDL, necroinflammatory foci and lymphocytic infiltration are obviously less than in controls

Gene & Allele Details

Allele Symbol Tlr4Lps-d
Allele Name defective lipopolysaccharide response
Common Name(s) TLR4-Mu; Tlr4-; Tlr4d; TlrLps-d; lpsd;
Strain of OriginC3H/HeJ
Gene Symbol and Name Tlr4, toll-like receptor 4
Chromosome 4
Gene Common Name(s) ARMD10; CD284; Lps; RAS-like, family 2, locus 8; Rasl2-8; TOLL; hToll; lipopolysaccharide response;
General Note C3H/HeJ mice carry this allele. Various combinations of Lps-associated traits have been followed in crosses between C3H/HeJ and other C3H substrains, and the traits have in all cases segregated together (J:30692, J:5557, J:5593, J:5938). Some of the traits show dominance of the Tlr4lps-n allele; others, including Tlr4Lps-d, show codominance.

Genbank ID for this allele: AF095353

Molecular Note This allele corresponds to a mutation in the third exon of the gene. A C to A substitution at nucleotide position 2342 results in an amino acid substitution that replaces proline with histidine at position 712. [MGI Ref ID J:51522] [MGI Ref ID J:53519] [MGI Ref ID J:57938]

Control Information

  Allele   Control
 Tlr4Lps-d  001026 BALB/cByJ
 
  Considerations for Choosing Controls
  Control Pricing Information for JAX® GEMM® Strains

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying   Tlr4Lps-d allele
005973   C3Bir.129P2(B6)-Il10C3Bir/LtJ
004326   C3Bir.129P2(B6)-Il10tm1Cgn/Lt
003968   C3Bir.129P2(B6)-Il10tm1Cgn/LtJ
000659   C3H/HeJ
005972   C3H/HeJBirLtJ
View Strains carrying   Tlr4Lps-d     (5 strains)

Strains carrying other alleles of Tlr4
007227   B6.B10ScN-Tlr4lps-del/JthJ
003752   C57BL/10ScNJ
View Strains carrying other alleles of Tlr4     (2 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report
JAX® NOTES, Summer 2005; 498. Toll-like Receptor JAX® Mice for Immunological Research.

Animal Health Reports

Room Number           AX8

Research Applications

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

Tlr4Lps-d related

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers (Tlr deficiency)
Immunodeficiency (Tlr deficiency)
Inflammation (Tlr deficiency)

References

Additional References

Price and Supply Information

Strain Name: C.C3-Tlr4Lps-d/J
Stock Number: 002930

Price Details

IMPORTANT NOTE: Prices are based on shipping destination. The shipping destinations are:

*Pricing for Shipping Destination selected:

        USA, Canada and Mexico

Price(s) in US dollars ($)Genotype(s) Provided
3-5 weeks $60.50Homozygous for Tlr4Lps-dFemale
6 weeks $62.95Homozygous for Tlr4Lps-dFemale
7 weeks $65.40Homozygous for Tlr4Lps-dFemale
8 weeks $67.85Homozygous for Tlr4Lps-dFemale
3-5 weeks $60.50Homozygous for Tlr4Lps-dMale
6 weeks $62.95Homozygous for Tlr4Lps-dMale
7 weeks $65.40Homozygous for Tlr4Lps-dMale
8 weeks $67.85Homozygous for Tlr4Lps-dMale
Pair $125.90Homozygous for Tlr4Lps-d x Homozygous for Tlr4Lps-d

Supply Details

Standard SupplyLevel 4. Up to 10 mice. Larger quantities or custom orders arranged upon request. Expected delivery up to one to three months.
Supply Notes Histology and Tissue Collection Services are available for all JAX® Mice strains. For more information, please contact Customer Service at orderquest@jax.org or 1-800-422-6423.
Shipped at a specific age in weeks. Mice at a precise age in days, littermates and retired breeders are also available.
Strains that must be genotyped are not available until five to seven weeks of age.
LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.
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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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