Strain Name:

B6;129S-Ldlrap1tm1Her/J

Stock Number:

005212

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Availability:

Cryopreserved - Ready for recovery

Other products are available, see Purchasing Information for Cryopreserved Embryos

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

Former Names B6;129S-AA691260tm1Her/J    (Changed: 12-JAN-05 )
B6;129S6-AA691260tm1Her/J    (Changed: 15-DEC-04 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation?+N1p (12-DEC-04)
Generation Definitions
 
Donating InvestigatorDr. Joachim Herz,   Univ of Texas Southwest Med Ctr Dallas

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of liver tissue. Low density lipoproteins (LDL) plasma levels are elevated in homozygous mutant mice. Mice homozygous for the mutant allele exhibit mild hypercholesterolemia when fed a chow diet. Low density lipoprotein-cholesterol, LDL-C, plasma levels are elevated 11 fold when homozygous mutant mice are fed the Paigen high cholesterol diet (1.25% cholesterol, 7.5% cocoa butter, 7.5% casein, 0.5% cholic acid) and 4.7 fold when fed the Western diet (0.2% cholesterol). The circulation clearance rate of radiolabeled LDL is reduced by half in mice homozygous for the mutant allele. Immunofluorescence microscopic analysis of liver tissue reveals abnormal LDLR localization to the sinsusoidal membrane. This mutant mouse strain may be useful in studies of autosomal recessive hypercholesterolemia.

Development
A targeting vector containing a loxP and FRT site flanked neomycin resistance gene and 2 tandemly arranged herpes simplex virus thymidine kinase genes was used to disrupt exon 4. The construct was electroporated into 129S6/SvEvTac derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. Heterozygote were bred to generate homozygotes.

Control Information

  Control
   See control note: Wildtypes from the colony or B6129SF1 mice (Stock No. 101043) may be used as controls.
   Wild-type from the colony
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Hypercholesterolemia, Autosomal Recessive; ARH
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Ldlrap1tm1Her/Ldlrap1tm1Her

        involves: 129S6/SvEvTac
  • homeostasis/metabolism phenotype
  • abnormal circulating LDL cholesterol level
    • LDL clearance is slowed   (MGI Ref ID J:84694)
    • increased circulating LDL cholesterol level
      • on a chow diet, plasma LDL levels were higher than those in wild-type mice but lower than those in Ldlrtm1Her homozygous mutant mice   (MGI Ref ID J:84694)
      • little LDL accumulation on a normal diet   (MGI Ref ID J:84694)
      • on high cholesterol diets most plasma cholesterol is LDL   (MGI Ref ID J:84694)
  • increased circulating cholesterol level
    • plasma cholesterol is only mildly elevated (83mg/dl) on a normal diet   (MGI Ref ID J:84694)
    • increased circulating LDL cholesterol level
      • on a chow diet, plasma LDL levels were higher than those in wild-type mice but lower than those in Ldlrtm1Her homozygous mutant mice   (MGI Ref ID J:84694)
      • little LDL accumulation on a normal diet   (MGI Ref ID J:84694)
      • on high cholesterol diets most plasma cholesterol is LDL   (MGI Ref ID J:84694)
  • increased circulating triglyceride level
    • plasma triglycerides increase more on a "wetern" diet than in Ldlrtm1Her homozygous mutant mice   (MGI Ref ID J:84694)
View Research Applications

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

Ldlrap1tm1Her related

Cardiovascular Research
Hypercholesterolemia

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ldlrap1tm1Her
Allele Name targeted mutation 1, Joachim Herz
Allele Type Targeted (knock-out)
Common Name(s) Arh-;
Mutation Made By Christopher Jones,   UT Southwestern Medical Center at Dallas
Strain of Origin129S6/SvEvTac
ES Cell Line NameSM1
ES Cell Line Strain129S6/SvEvTac
Gene Symbol and Name Ldlrap1, low density lipoprotein receptor adaptor protein 1
Chromosome 4
Gene Common Name(s) AA691260; ARH; ARH1; ARH2; FHCB1; FHCB2; RGD1563417; expressed sequence AA691260;
Molecular Note Exon 4 was replaced with a neomycin selection cassette that was flanked by both loxP and FRT sites. The deletion of exon 4 disrupts sequence encoding the PTB domain. Normal protein was undetected in homozygous mutant mice by Western blot analysis using an antibody directed against the PTB domain. If aberrant splicing were to occur between exons 3 and 5, a frameshift mutation and resultant nonsense mutation would putatively preclude the translation of the clathrin and adapter protein complex (AP-2) binding sites. [MGI Ref ID J:84694]

Genotyping

Genotyping Information

Genotyping Protocols

Ldlrap1tm1Her, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Jones C; Hammer RE; Li WP; Cohen JC; Hobbs HH; Herz J. 2003. Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia. J Biol Chem 278(31):29024-30. [PubMed: 12746448]  [MGI Ref ID J:84694]

Additional References

Ldlrap1tm1Her related

Fang L; Garuti R; Kim BY; Wade JB; Welling PA. 2009. The ARH adaptor protein regulates endocytosis of the ROMK potassium secretory channel in mouse kidney. J Clin Invest 119(11):3278-89. [PubMed: 19841541]  [MGI Ref ID J:154598]

Jones C; Garuti R; Michaely P; Li WP; Maeda N; Cohen JC; Herz J; Hobbs HH. 2007. Disruption of LDL but not VLDL clearance in autosomal recessive hypercholesterolemia. J Clin Invest 117(1):165-74. [PubMed: 17200716]  [MGI Ref ID J:117439]

Lagace TA; Curtis DE; Garuti R; McNutt MC; Park SW; Prather HB; Anderson NN; Ho YK; Hammer RE; Horton JD. 2006. Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and inlivers of parabiotic mice. J Clin Invest 116(11):2995-3005. [PubMed: 17080197]  [MGI Ref ID J:114949]

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 & HusbandryThis strain is maintained as a heterozygote.
Diet Information LabDiet® 5K52/5K67

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* $2450.00
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.

Embryos

Price (US dollars $)
Frozen Embryo $1600.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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 11 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* $3185.00
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.

Embryos

Price (US dollars $)
Frozen Embryo $2080.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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 11 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
   See control note: Wildtypes from the colony or B6129SF1 mice (Stock No. 101043) may be used as controls.
   Wild-type from the colony
 
  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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