| |||||||
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote (Female x Male) Species laboratory mouse Generation N?+1F4 (10-DEC-07) Donating Investigator Dr. 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 | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
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
| Allele Symbol | Pdzk1tm1Dls | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, David L Silver | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | PDZK1-; | ||
| Mutation Made By | Dr. David Silver, Albert Einstein College of Medicine | ||
| Strain of Origin | 129S6/SvEvTac | ||
| ES Cell Line Name | iTL1 | ||
| ES Cell Line Strain | 129S6/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 Protocols
Pdzk1tm1Dls, SEP PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
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]
Pdzk1tm1Dls relatedWang 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]
Animal Health Reports
Room Number FGB29
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred together. Mating System Homozygote x Homozygote (Female x Male) Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $155.70 Female or Male Homozygous for Pdzk1tm1Dls *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $311.40 Homozygous for Pdzk1tm1Dls x Homozygous for Pdzk1tm1Dls
| Supply Notes |
|
|---|
| Pricing for International shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $202.50 Female or Male Homozygous for Pdzk1tm1Dls *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $404.90 Homozygous for Pdzk1tm1Dls x Homozygous for Pdzk1tm1Dls
| Supply Notes |
|
|---|
| Standard Supply | Repository-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 | ||
|---|---|---|
| 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. | ||
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. THE LABORATORY EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.
In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.
MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.
Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.