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| These mice may be useful in studies of lipid homeostasis, cholesterol metabolism, apolipoprotein function, and statin treatment for hypercholesterolemia. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote (Female x Male) 01-JUL-09 Species laboratory mouse Generation N1+N2F8 (30-JUN-11)
Generation DefinitionsDonating Investigator Dr. Jay D. Horton, Univ of Texas SW Med Center at Dallas Description
Homozygous mice are viable and fertile with no behavioral abnormalities. No expression of the endogenous RNA or protein is observed in liver. Homozygotes have reduced plasma cholesterol levels; apolipoprotein B (apoB)-containing low-density liproprotein (LDL) is nearly undetectable and apolipoprotein E (apoE)-containing high density liproprotein (HDL) levels are reduced 30%. Homozygotes show increased hepatic LDL-receptor (LDLR) protein (but not RNA) expression. Homogygous mice also have accelerated clearance of circulating cholesterol. Lovastatin addition to the diet of homozygous mice results in further increased hepatic LDLR and LDL clearance from the blood. Heterozygous mice have intermediate plasma cholesterol and LDL clearance. This mouse may be useful in studies of lipid homeostasis, cholesterol metabolism, apolipoprotein function, and statin treatment for hypercholesterolemia.Development
A targeting vector was designed to replace the region spanning from the C-terminal region of exon 2 through exon 4 of the endogenous gene with a neomycin resistance cassette. The construct was electroporated into 129S6/SvEvTac-derived SM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric males were bred to C57BL/6J females. Heterozygous offspring were crossed to generate homozygous mice.
Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
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Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Phenotype
Phenotype Information
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Hypercholesterolemia, Autosomal Dominant, 3; HCHOLA3 (PCSK9)
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Pcsk9tm1Jdh/Pcsk9tm1Jdh
involves: 129S6/SvEvTac
- homeostasis/metabolism phenotype
- decreased circulating cholesterol level
- decreased circulating HDL cholesterol level
- 30% reduction in plasma HDL cholesterol levels (MGI Ref ID J:97836)
- decreased circulating LDL cholesterol level
- nearly undetectable levels of plasma LDL cholesterol levels (MGI Ref ID J:97836)
- 5-fold increase in the rate of labeled LDL cholesterol clearance from plasma (12 min to clear 50% of LDL versus more than 60 min in wildtype) (MGI Ref ID J:97836)
- additional 2-fold increase in the rate of labeled LDL cholesterol clearance from plasma when lovastatin was added to the diet (MGI Ref ID J:97836)
This mouse can be used to support research in many areas including:
Cardiovascular Research
Atherosclerosis
Hypercholesterolemia
Hypocholesterolemia
Other
altered fat metabolism
altered lipoprotein profile
Metabolism Research
Lipid Metabolism
Neurobiology Research
Alzheimer's Disease
Research Tools
Cardiovascular Research
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Pcsk9tm1Jdh | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Jay D Horton | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Pcsk9-; | ||
| Mutation Made By | Dr. Jay Horton, Univ of Texas SW Med Center at Dallas | ||
| Strain of Origin | 129S6/SvEvTac | ||
| ES Cell Line Name | SM1 | ||
| ES Cell Line Strain | 129S6/SvEvTac | ||
| Gene Symbol and Name | Pcsk9, proprotein convertase subtilisin/kexin type 9 | ||
| Chromosome | 4 | ||
| Gene Common Name(s) | AI415265; AI747682; FH3; HCHOLA3; LDLCQ1; NARC-1; NARC1; PC9; expressed sequence AI415265; expressed sequence AI747682; | ||
| Molecular Note | A targeting vector containing a neomycin resistance gene was inserted to replace the 3' half of exon 2 through exon 4. Northern blot of mutant livers confirmed absence of transcript. Immunoblot of livers further confirmed absence of protein. [MGI Ref ID J:97836] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Pcsk9tm1Jdh, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Rashid S; Curtis DE; Garuti R; Anderson NN; Bashmakov Y; Ho YK; Hammer RE; Moon YA; Horton JD. 2005. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci U S A 102(15):5374-9. [PubMed: 15805190] [MGI Ref ID J:97836]
Additional References
Pcsk9tm1Jdh relatedJonas MC; Costantini C; Puglielli L. 2008. PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1. EMBO Rep 9(9):916-22. [PubMed: 18660751] [MGI Ref ID J:138995]
Jonas MC; Pehar M; Puglielli L. 2010. AT-1 is the ER membrane acetyl-CoA transporter and is essential for cell viability. J Cell Sci 123(Pt 19):3378-88. [PubMed: 20826464] [MGI Ref ID J:182823]
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]
Langhi C; Le May C; Gmyr V; Vandewalle B; Kerr-Conte J; Krempf M; Pattou F; Costet P; Cariou B. 2009. PCSK9 is expressed in pancreatic delta-cells and does not alter insulin secretion. Biochem Biophys Res Commun 390(4):1288-93. [PubMed: 19878649] [MGI Ref ID J:155603]
Le May C; Kourimate S; Langhi C; Chetiveaux M; Jarry A; Comera C; Collet X; Kuipers F; Krempf M; Cariou B; Costet P. 2009. Proprotein convertase subtilisin kexin type 9 null mice are protected from postprandial triglyceridemia. Arterioscler Thromb Vasc Biol 29(5):684-90. [PubMed: 19265033] [MGI Ref ID J:161830]
Mbikay M; Sirois F; Mayne J; Wang GS; Chen A; Dewpura T; Prat A; Seidah NG; Chretien M; Scott FW. 2010. PCSK9-deficient mice exhibit impaired glucose tolerance and pancreatic islet abnormalities. FEBS Lett 584(4):701-6. [PubMed: 20026049] [MGI Ref ID J:157666]
Sun H; Samarghandi A; Zhang N; Yao Z; Xiong M; Teng BB. 2012. Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein B and prevents its intracellular degradation, irrespective of the low-density lipoprotein receptor. Arterioscler Thromb Vasc Biol 32(7):1585-95. [PubMed: 22580899] [MGI Ref ID J:186176]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred together. Mating System Homozygote x Homozygote (Female x Male) 01-JUL-09 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $177.00 Female or Male Homozygous for Pcsk9tm1Jdh
Price per Pair (US dollars $) Pair Genotype $354.00 Homozygous for Pcsk9tm1Jdh x Homozygous for Pcsk9tm1Jdh Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $230.10 Female or Male Homozygous for Pcsk9tm1Jdh
Price per Pair (US dollars $) Pair Genotype $460.20 Homozygous for Pcsk9tm1Jdh x Homozygous for Pcsk9tm1Jdh Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
|
|
|
Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| 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.Ordering Information
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