Strain Name:

B6.129S4-Asgr1tm1Sau/SaubJxmJ

Stock Number:

009105

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Availability:

Cryopreserved - Ready for recovery

These mice harbor a targeted mutation of the asialoglycoprotein receptor 1 locus that abolishes endogenous gene expression. Impaired hepatic clearance of asialoglycoproteins is observed.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
 
Donating Investigator Jamey D Marth,   Burnham Inst at Univ Calif Santa Barbara

Description
These mice harbor a targeted mutation of the asialoglycoprotein receptor 1 (Asgr1; also known as hepatic lectin-1 [HL-1]) locus that abolishes endogenous gene expression. Homozygous mice (Asgr1-/- mice) are viable and fertile, with no plasma asialoglycoprotein or platelet level abnormalities. Asgr1-/- mice have impaired hepatic clearance of asialoglycoproteins (exogenous desialylated glycoproteins). Homozygous mice also exhibit altered von Willebrand factor (vWF) levels (increased plasma vWF and reduced hepatocyte-associated vWF). Asgr1-deficiency is associated with reduced bleeding time and enhanced platelet survival. When injected with Streptococcus pneumoniae, homozygous mice have increased susceptibility to infection and mortality (severe intravascular coagulation due to impaired clearance of prothrombotic components: platelets and vWF desialylated by the bacterium's neuraminidase are not eliminated from circulation). These Asgr1 mutant mice may be useful in studying the function of the hepatocyte Ashwell-Morell asialoglycoprotein receptor and its ligands (asialoglycoproteins, von Willebrand factor (vWF) and platelets) in blood coagulation and thrombosis, as well as the capture and endocytosis of a wide range of exogenously administered, potentially deleterious circulating glycoproteins.

Development
A targeting vector was designed by the laboratory of Dr. Brian Sauer (while at Oklahoma Medical Research Foundation) to delete the MHL-1 major subunit coding region in exon 2 of the asialoglycoprotein receptor 1 (Asgr1; also known as hepatic lectin-1 [HL-1]) locus and insert a loxp-flanked PGKneo cassette (followed by a synthetic lox511 site) two nucleotides before the Asgr1 translational start site. This construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric offspring were bred with C57BL/6J mice to generate the mutant colony. These MHL-1 null (or Asgr1 null) mice were backcrossed for at least six generations to C57BL/6J and then sent to Dr. Jamey D. Marth (at University of California San Diego). The donating investigator reported that these Asgr1 null mice were backcrossed to C57BL/6NHsd mice (see SNP note below) for at least six generations. Upon arrival at The Jackson Laboratory Repository, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6N genetic background.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, at least 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Information

  Control
   005304 C57BL/6NJ
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Asgr1tm1Sau/Asgr1tm1Sau

        B6.129S4-Asgr1tm1Sau
  • mortality/aging
  • increased sensitivity to induced morbidity/mortality
    • following infection with S. pneumoniae, mice exhibit decreased survival compared to similarly treated wild-type mice   (MGI Ref ID J:136946)
  • homeostasis/metabolism phenotype
  • decreased bleeding time   (MGI Ref ID J:136946)
  • immune system phenotype
  • increased susceptibility to bacterial infection
    • following infection with S. pneumoniae, mice exhibit decreased survival compared to similarly treated wild-type mice   (MGI Ref ID J:136946)
    • following infection with S. pneumoniae, mice exhibit hemorrhage of the spleen, increased hepatocyte cell death, and increased vascular occlusion and fibrin deposition in the kidney and liver compared to similarly treated wild-type mice   (MGI Ref ID J:136946)
View Research Applications

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

Cardiovascular Research
Vascular Defects
      Thrombosis
      platelet defect

Developmental Biology Research
Internal/Organ Defects
      liver

Hematological Research
Clotting Defects
Platelet Defects
      Alterations in platelet aggregation
      thrombocytopenia

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
      genes regulating susceptibility to infectious disease and endotoxin

Internal/Organ Research
Liver Defects

Research Tools
Cardiovascular Research
Genetics Research
      Tissue/Cell Markers
      Tissue/Cell Markers: hepatocytes
Hematological Research
Immunology, Inflammation and Autoimmunity Research
      genes regulating susceptibility to infectious disease and endotoxin
Internal/Organ Research
Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Asgr1tm1Sau
Allele Name targeted mutation 1, Brian Sauer
Allele Type Targeted (Null/Knockout)
Mutation Made ByDr. Brian Sauer,   Stowers Institute for Medical Research
Strain of Origin129S4/SvJae
Gene Symbol and Name Asgr1, asialoglycoprotein receptor 1
Chromosome 11
Gene Common Name(s) ASGPR; ASGPR1; ASGR; Asgr; Asgr-1; CLEC4H1; HL-1; RATRHL1; RHL1; asialoglycoprotein receptor complex;
Molecular Note The coding region of exon 2 was replaced with a floxed neo cassette with an additional 3' lox511 site. [MGI Ref ID J:137342]

Genotyping

Genotyping Information

Genotyping Protocols

Asgr1tm1Sau, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Grewal PK; Uchiyama S; Ditto D; Varki N; Le DT; Nizet V; Marth JD. 2008. The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat Med 14(6):648-55. [PubMed: 18488037]  [MGI Ref ID J:136946]

Rumjantseva V; Grewal PK; Wandall HH; Josefsson EC; Sorensen AL; Larson G; Marth JD; Hartwig JH; Hoffmeister KM. 2009. Dual roles for hepatic lectin receptors in the clearance of chilled platelets. Nat Med 15(11):1273-80. [PubMed: 19783995]  [MGI Ref ID J:154297]

Soukharev S; Miller JL; Sauer B. 1999. Segmental genomic replacement in embryonic stem cells by double lox targeting. Nucleic Acids Res 27(18):e21. [PubMed: 10471751]  [MGI Ref ID J:137342]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   005304 C57BL/6NJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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