Strain Name:

B6;129S6-Pdzk1tm1Dls/J

Stock Number:

006208

Availability:

Repository- Live

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered Mutant Mice.
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
GenerationN?+1F4 (10-DEC-07)
 
Donating InvestigatorDr. David Silver,   Albert Einstein College of Medicine

Description
Mice homozygous for this targeted mutation are viable and fertile. Liver tissue from homozygous mutant mice lacks endogenous protein expression. Homozygotes, but not heterozygotes, have significantly decreased (~85-95%) hepatic high density lipoprotein (HDL) receptor scavenger receptor B-I (SR-BI) levels. This decrease is further exacerbated following diet supplementation with the PPAR-alpha activator fenofibrate. These mice may be useful in studies of cardiovascular health and atherosclerosis, lipid metabolism, SR-B1 regulation, kidney function, as well as kidney transporter (e.g. urate transporter) regulation and liver organic anion transport.

Development
A targeting vector was designed to replace exon 1 and part of intron 1 of the endogenous gene with a neomycin resistance cassette. This construct was electroporated into 129S6/SvEvTac-derived CSL3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric mice were bred with C57BL/6J to generate heterozygous mice on this mixed B6;129S6 genetic background. Heterozygotes were then bred together for many generations prior to arrival at The Jackson Laboratory.

Control Information

  Control
   101043 B6129SF1/J (approximate)
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Pdzk1tm1Dls/Pdzk1tm1Dls

        involves: 129S6/SvEvTac * C57BL/6J
  • homeostasis/metabolism phenotype
  • abnormal circulating protein level (MGI Ref ID J:107125)
    • fractional uptake rate of BSP is reduced by 25% in mutants compared with wild-type and plasma half life is increased correspondingly be 25% in knockouts
  • liver/biliary system phenotype
  • abnormal liver morphology (MGI Ref ID J:107125)
    • scavenger receptor B, type I expression and function in mutant livers are markedly reduced in knockouts
    • distribution of organic anion transporting protein 1A1 is predominantly in intracellular structures, while in wild-type it has a basolateral distribution
View Research Applications

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

Cardiovascular Research
Atherosclerosis
Other (altered lipoprotein profile)

Cell Biology Research
Channel and Transporter Defects

Internal/Organ Research
Kidney Defects
Liver Defects

Metabolism Research
Lipid Metabolism

Research Tools
Cardiovascular Research
Metabolism Research

Genes & Alleles

Gene & Allele Information

Allele Symbol Pdzk1tm1Dls
Allele Name targeted mutation 1, David L Silver
Allele Type Targeted (knock-out)
Common Name(s) PDZK1-;
Mutation Made ByDr. David Silver,   Albert Einstein College of Medicine
Strain of Origin129S6/SvEvTac
ES Cell Line NameiTL1
ES Cell Line Strain129S6/SvEvTac
Gene Symbol and Name Pdzk1, PDZ domain containing 1
Chromosome 3
Gene Common Name(s) 1700023D20Rik; 2610507N21Rik; 4921513F16Rik; AI267131; AI314638; AL022680; CAP70; CLAMP; D3Ertd537e; DNA segment, Chr 3, ERATO Doi 537, expressed; NHERF3; PDZD1; RIKEN cDNA 1700023D20 gene; RIKEN cDNA 2610507N21 gene; RIKEN cDNA 4921513F16 gene; expressed sequence AI267131; expressed sequence AI314638; expressed sequence AL022680; mPDZK1;
Molecular Note Exon 1, containing the ATG, and part of intron 1 were replaced by neomycin resistance cassette. Western blot of mutant liver lysates confirmed absence of protein. [MGI Ref ID J:100280]

Genotyping

Genotyping Information

Genotyping Protocols

Pdzk1tm1Dls, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Lan D; Silver DL. 2005. Fenofibrate induces a novel degradation pathway for scavenger receptor B-I independent of PDZK1. J Biol Chem 280(24):23390-6. [PubMed: 15837786]  [MGI Ref ID J:100280]

Additional References

Pdzk1tm1Dls related

Wang P; Wang JJ; Xiao Y; Murray JW; Novikoff PM; Angeletti RH; Orr GA; Lan D; Silver DL; Wolkoff AW. 2005. Interaction with PDZK1 is required for expression of organic anion transporting protein 1A1 on the hepatocyte surface. J Biol Chem 280(34):30143-9. [PubMed: 15994332]  [MGI Ref ID J:107125]

Zhou H; Li Z; Silver DL; Jiang XC. 2006. Cholesteryl ester transfer protein (CETP) expression enhances HDL cholesteryl ester liver delivery, which is independent of scavenger receptor BI, LDL receptor related protein and possibly LDL receptor. Biochim Biophys Acta 1761(12):1482-8. [PubMed: 17055779]  [MGI Ref ID J:118151]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.
Mating SystemHomozygote x Homozygote         (Female x Male)
Diet Information LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice*GenderGenotypes Provided
Individual Mouse Price $155.70Female or MaleHomozygous for Pdzk1tm1Dls
Pairs /Price*Pair Genotype
$311.40Homozygous for Pdzk1tm1Dls x Homozygous for Pdzk1tm1Dls
*Price(s) in US dollars ($)

Additional Supply Details

Supply Notes

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice*GenderGenotypes Provided
Individual Mouse Price $202.50Female or MaleHomozygous for Pdzk1tm1Dls
Pairs /Price*Pair Genotype
$404.90Homozygous for Pdzk1tm1Dls x Homozygous for Pdzk1tm1Dls
*Price(s) in US dollars ($)

Additional Supply Details

Supply Notes

Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes

Control Information

  Control
   101043 B6129SF1/J (approximate)
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls
  USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
  International - Control Pricing Information for Genetically Engineered Mutant Strains.

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