Overview

This C57BL/10 substrain was inbred at NIH until it was sent back to The Jackson Laboratory in 2000. These mice, carrying a spontaneous deletion of the Tlr4 gene, serve as a common genetic background for histocompatibility congenic and mutant strains.

Genetic overview

Genetic Background	Generation
	F131+34pN1F13 (2020-01-20 00:00:00)

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Research Applications

Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$278.00 Domestic price for female 4-week

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Details

Important Note

This strain is homozygous for the defective lipopolysaccharide response, deletion allele Tlr4^lps-del.

Detailed Description

The breeder pair of C57BL/10ScN mice, obtained from NIH, that were the progenitors of all mice of this strain at The Jackson Laboratory were tested by PCR analysis for the spontaneous Il12rb2 mutation described by Poltorak et al. (J. Immunol. 167:2106-2111, 2001) and found to carry only the wild type Il12rb2 allele. C57BL/10ScN mice have a deletion of the Tlr4 gene that results in absence of both mRNA and protein and thus in defective response to LPS stimulation. Tlr4^lps-del differs from the Tlr4^Lps-d mutation of C3H/HeJ mice, 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 other mouse strains.

Development

The C57BL/6 and C57BL/10 sublines of the C57BL mouse line diverged sometime prior to 1937. The C57BL/10 subline was passed from Clarence Little to J.P. Scott (lab code Sc) at F26 and from Scott to George Snell (Sn) at F35 around 1947. In 1953, Snell sent mice of this line, C57BL/10ScSn (also known as C57BL/10Sn) to the National Institutes of Health (N) (Vogel et al. 1979), where it was initially designated C57BL/10ScSnN; however, Snell's lab code was dropped early on, and the strain has been called C57BL/10ScN for most of its history at NIH (Hansen et al. 2000). Clarence Reeder (Cr) began maintaining mice of this line at the Frederick Cancer Research Center, Frederick, MD in 1961 (Vogel et al. 1979), and mice distributed from this colony were designated C57BL/10ScNCr (Hansen et al. 2000). The breeding stock at the Cancer Research Center is replenished regularly with C57BL/10ScN from NIHAGR (Hansen et al. 2000), and mice of both colonies are screened annually for 14 biochemical markers and every two years by skin grafting; therefore, C57BL/10ScN, C57BL/10ScNCr and, presumably, C57BL/10ScCr are names for the same subline of C57BL/10.

A pedigreed sibling pair of C57BL/10ScN mice obtained in August, 2000 at N130 from the NIH foundation colony was used to found the colony now maintained at The Jackson Laboratory.

Selected References

Petkov PM; Cassell MA; Sargent EE; Donnelly CJ; Robinson P; Crew V; Asquith S; Haar RV; Wiles MV. 2004. Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse. Genomics 83(5):902-11PubMed: 15081119 MGI: J:89298

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Genetics

Tlr4^lps-del

Allele Symbol: Tlr4^lps-del

Allele Name	defective lipopolysaccharide response, deletion
Allele Type	Spontaneous
Allele Synonym(s)	defective lipopolysaccharide response, deletion; Tlr4^lps-del
Gene Symbol and Name	Tlr4, toll-like receptor 4
Gene Synonym(s)	ARMD10; Rasl2-8; Rasl2-8; CD284; lipopolysaccharide response; Lps; lipopolysaccharide response; Lps; TLR-4; RAS-like, family 2, locus 8; TOLL
Strain of Origin	C57BL/10ScN
Chromosome	4
General Note	C57BL/10ScN, C57BL/10ScNJ, and C57BL10/ScCr 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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Tlr4^lps-del related

Immunology, Inflammation and Autoimmunity Research
- Inflammation
  - Tlr deficiency
- Immunodeficiency
  - Tlr deficiency
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - Tlr deficiency

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Tlr4^lps-del/Tlr4^lps-del
C57BL/10ScN

adipose tissue phenotype

decreased percent body fat/body weight
- 70% less body fat

pigmentation phenotype

abnormal retinal pigment epithelium morphology
- increased number of proliferating cells in the retinal pigment cell layer at 6 days of age

respiratory system phenotype

abnormal pulmonary alveolar duct morphology
- enlarged air spaces distal to the terminal bronchioles

abnormal pulmonary alveolus morphology
- destruction of normal alveolar structures

enlarged lung
- significantly increased lung volume at 3 months of age in contrast to normal body weights through 12 months

skeleton phenotype

increased bone mass
- larger bones at 20-24 weeks of age

increased bone mineral content
- greater mineral content at 20-24 weeks

vision/eye phenotype

abnormal retinal layer morphology

abnormal retinal pigment epithelium morphology
- increased number of proliferating cells in the retinal pigment cell layer at 6 days of age

abnormal retinal progenitor cell morphology
- FGF-2 injection is required for a similar effect after 15 days of age
- more proliferating cells in the retina at 6 days of age
- neuronal differentiation of precursors

abnormal retinal rod bipolar cell morphology
- growth factor treatment enhances proliferation
- increased differentiation at around 13 days of age

abnormal retinal rod cell morphology
- growth factor treatment enhances proliferation
- increased differentiation of rod photoreceptors at around 13 days of age

cardiovascular system phenotype

rectal hemorrhage
- rectal bleeding after 7 days of dextran sodium sulfate treatment is reduced relative to controls

digestive/alimentary phenotype

rectal hemorrhage
- rectal bleeding after 7 days of dextran sodium sulfate treatment is reduced relative to controls

hematopoietic system phenotype

increased spleen weight
- spleen weight elevated with dextran sodium sulfate treatment relative to controls

immune system phenotype

increased spleen weight
- spleen weight elevated with dextran sodium sulfate treatment relative to controls

nervous system phenotype

abnormal retinal rod bipolar cell morphology
- growth factor treatment enhances proliferation
- increased differentiation at around 13 days of age

abnormal retinal rod cell morphology
- growth factor treatment enhances proliferation
- increased differentiation of rod photoreceptors at around 13 days of age

Genotype: Tlr4^lps-del/Tlr4^lps-del
involves: C57BL/10ScN

cellular phenotype

abnormal neuron differentiation
- improved differentiation of progenitor cells into neurons
- survival of newly formed neurons is reduced

nervous system phenotype

abnormal neuron differentiation
- improved differentiation of progenitor cells into neurons
- survival of newly formed neurons is reduced

CNS ischemia
- improved neurological score relative to controls after ischemia/reperfusion
- reduced infarct size relative to controls at 24 hours after ischemia/reperfusion

homeostasis/metabolism phenotype

abnormal circulating enzyme level
- increased HO-1 expression
- myeloperoxidase levels are reduced after 90 minutes of liver ischemia followed by 6 hours of reperfusion

abnormal tumor necrosis factor level
- diminished TNF alpha expression after 90 minutes of liver ischemia followed by 6 hours of reperfusion

decreased circulating alanine transaminase level
- serum levels decreased after 90 minutes of liver ischemia followed by 6 hours of reperfusion

immune system phenotype

abnormal tumor necrosis factor level
- diminished TNF alpha expression after 90 minutes of liver ischemia followed by 6 hours of reperfusion

decreased interleukin-10 secretion
- production is suppressed in response to E coli with or without adenosine

decreased interleukin-6 secretion
- production is suppressed in response to E coli

Phenotype Information

References

Petkov PM; Cassell MA; Sargent EE; Donnelly CJ; Robinson P; Crew V; Asquith S; Haar RV; Wiles MV. 2004. Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse. Genomics 83(5):902-11PubMed: 15081119 MGI: J:89298

Additional References

Khanolkar A; Hartwig SM; Haag BA; Meyerholz DK; Harty JT; Varga SM. 2009. Toll-like receptor 4 deficiency increases disease and mortality after mouse hepatitis virus type 1 infection of susceptible C3H mice. J Virol 83(17):8946-56PubMed: 19553337 MGI: J:153918
Park HS; Back YW; Shin KW; Bae HS; Lee KI; Choi HG; Choi S; Lee HH; Choi CH; Park JK; Kim HJ. 2019. Mycobacterium tuberculosis Rv3463 induces mycobactericidal activity in macrophages by enhancing phagolysosomal fusion and exhibits therapeutic potential. Sci Rep 9(1):4246PubMed: 30862819 MGI: J:275606
Yu LX; Yan L; Yang W; Wu FQ; Ling Y; Chen SZ; Tang L; Tan YX; Cao D; Wu MC; Yan HX; Wang HY. 2014. Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein. Nat Commun 5:5256PubMed: 25348021 MGI: J:278392
Kuo PJ; Rau CS; Wu SC; Lu TH; Wu YC; Chien PC; Wu CJ; Lin CW; Tsai CW; Hsieh CH; Huang CY. 2019. Metagenomic analysis of the effects of toll-like receptors on bacterial infection in the peritoneal cavity following cecum ligation and puncture in mice. PLoS One 14(7):e0220398PubMed: 31348811 MGI: J:279705
Nath KA; Belcher JD; Nath MC; Grande JP; Croatt AJ; Ackerman AW; Katusic ZS; Vercellotti GM. 2018. Role of TLR4 signaling in the nephrotoxicity of heme and heme proteins. Am J Physiol Renal Physiol 314(5):F906-F914PubMed: 28978536 MGI: J:283214

Additional - Tlr4^lps-del related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Tlr4
- Separated PCR:Tlr4
- Genotyping resources and troubleshooting
Dietary Information
- New Diet as of March 2015: Lab Diet® 5K0Q (6% fat)
Mating System
- Sibling x Sibling
Appearance
- black
  Related Genotype: a/a
Citation
When using the C57BL/10ScNJ mouse strain in a publication, please include JAX stock #003752 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Inbred, 1 pair minimum will be supplied

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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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Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Development

Selected References

Tlr4lps-del

Allele Symbol: Tlr4lps-del

Disease Terms

Research Areas By Phenotype

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

Genotype: Tlr4lps-del related

Mammalian Phenotype Terms by Genotype

Genotype: Tlr4lps-del/Tlr4lps-delC57BL/10ScN

adipose tissue phenotype

pigmentation phenotype

respiratory system phenotype

skeleton phenotype

vision/eye phenotype

cardiovascular system phenotype

digestive/alimentary phenotype

hematopoietic system phenotype

immune system phenotype

nervous system phenotype

Genotype: Tlr4lps-del/Tlr4lps-delinvolves: C57BL/10ScN

cellular phenotype

nervous system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Phenotype Information

References

Additional References

Additional - Tlr4lps-del related

Genotyping Protocols

Dietary Information

Mating System

Appearance

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Tlr4^lps-del

Allele Symbol: Tlr4^lps-del

Genotype: Tlr4^lps-del related

Genotype: Tlr4^lps-del/Tlr4^lps-del
C57BL/10ScN

Genotype: Tlr4^lps-del/Tlr4^lps-del
involves: C57BL/10ScN

Additional - Tlr4^lps-del related