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Genes & Alleles

Tlr4;   Tlr4lps-del;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Spontaneous Mutation Mating System +/+ sibling x Heterozygote         (Female x Male) Species laboratory mouse Background Strain C57BL/6 Donor Strain C57BL/10ScN H2 Haplotype b Generation N6+ (12-AUG-08)

Appearance
black
Related Genotype: a/a

Strain Description
This spontaneous mutation is a 7 kb deletion in the Tlr4 gene, which results in absence of both mRNA and protein and thus exhibits a defective response to LPS stimulation. The functionally similar Tlr4^Lps-d mutation found in C3H/HeJ mice is a point mutation that causes an amino acid substitution. The allele for normal LPS response, Tlr4^lps-n, occurs in most other C3H and C57BL/10 substrains and most mouse strains. This strain may be used to study the Toll signalling pathway and susceptibility to Gram-negative bacterial infection.

Strain Development
Abnormal response to lipopolysaccharide was observed in the inbred strain C57BL/10ScN in the 1970s. The phenotype was subsequently identified as a mutation in the Tlr4 gene. This strain originated from the C57BL/10ScN colony at NCI Frederick and was transferred to the laboratory of Dr. James Thomas, University of Texas Southwestern Medical Center. The allele was introgressed into C57BL/6 by backcrossing for at least five generations. The strain was donated to The Jackson Laboratory Repository in 2008.

Related Disease (OMIM) Terms Toll-Like Receptor 4; TLR4

Mammalian Phenotype Terms assigned by genotype The following phenotype information may relate to a genetic background differing from this JAX® Mice strain. Tlr4lps-del/Tlr4lps-del         C57BL/10ScCr immune system phenotype abnormal cytokine secretion (MGI Ref ID J:88996) higher levels of Th1 and Th2 cytokines secreted at 4 weeks after infection with Leishmania major than in controls abnormal macrophage physiology (MGI Ref ID J:88996) poor activation of macrophage by Leishmania major increased susceptibility to bacterial infection (MGI Ref ID J:51522) response to endotoxin (LPS) prevented Leishmania major parasitic loads significantly higher than controls starting 24 hours after infection and persisting to 11 weeks after infection when controls are free of parasites behavior/neurological phenotype hyporesponsive to tactile stimuli (MGI Ref ID J:97819) attenuated mechanical allodynia after nerve injury increased thermal nociceptive threshold (MGI Ref ID J:97819) attenuated response to heat nervous system phenotype abnormal glial cell physiology (MGI Ref ID J:97819) glial activation after nerve injury reduced touch/vibrissae phenotype hyporesponsive to tactile stimuli (MGI Ref ID J:97819) attenuated mechanical allodynia after nerve injury increased thermal nociceptive threshold (MGI Ref ID J:97819) attenuated response to heat 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 homeostasis/metabolism phenotype decreased susceptibility to injury (MGI Ref ID J:97819) reduced spinal expression of TNF alpha, IFN gamma, IL-6 and IL-1 after injury glial activation after nerve injury reduced

Gene & Allele Details

Allele Symbol		Tlr4lps-del
Allele Name		defective lipopolysaccharide response, deletion
Common Name(s)		Tlr4-;
Strain of Origin		C57BL/10ScN
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		C57BL/10ScN mice carry this allele.
Molecular Note		This allele has been characterized by lack of mRNA owing to a deletion of the locus. 74723bp of genomic DNA sequence have been removed, apparently encompasing only the Tlr4 gene. [MGI Ref ID J:122203] [MGI Ref ID J:51522]

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.

Related Strains

Strains carrying   Tlr4^lps-del allele

003752

C57BL/10ScNJ

View Strains carrying   Tlr4^lps-del     (1 strain)

Strains carrying other alleles of Tlr4

002930	C.C3-Tlr4Lps-d/J
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 other alleles of Tlr4     (6 strains)

Additional Web Information

Congenic Nomenclature

Research Applications

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

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

Tlr4^lps-del related

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

References

Selected Reference(s)

Poltorak A; He X; Smirnova I; Liu MY; Huffel CV; Du X; Birdwell D; Alejos E; Silva M; Galanos C; Freudenberg M; Ricciardi-Castagnoli P; Layton B; Beutler B. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282(5396):2085-8. [PubMed: 9851930]  [MGI Ref ID J:51522]

Vogel SN; Hansen CT; Rosenstreich DL. 1979. Characterization of a congenitally LPS-resistant, athymic mouse strain. J Immunol 122(2):619-22. [PubMed: 368244]  [MGI Ref ID J:6086]

Additional References

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Price and Supply Information

Strain Name:	B6.B10ScN-Tlr4lps-del/JthJ
Stock Number:	007227

 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

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Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	This strain is included in the Mouse Mutant Resource collection.
Licensing	See General Terms and Conditions below
Control Information	View Control Information in Strain Details.

General Terms and Conditions

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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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