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| These mice may be useful in studies of lipid homeostasis, cholesterol metabolism, apolipoprotein function, and statin treatment for hypercholesterolemia. | |||||||||
Type Mutant Stock; Targeted Mutation; Mating System Heterozygote x Homozygote (Female x Male) Species laboratory mouse Generation N1+F3 (08-JAN-08) Donating Investigator Jay 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 | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Mammalian Phenotype Terms 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 (MGI Ref ID J:97836)
- plasma cholesterol levels were 48% lower than in wildtype, despite similar levels of plasma triglycerides
- plasma cholesterol levels decreased even more with the addition of lovastatin to the diet
- decreased circulating HDL cholesterol level (MGI Ref ID J:97836)
- 30% reduction in plasma HDL cholesterol levels
- decreased circulating LDL cholesterol level (MGI Ref ID J:97836)
- nearly undetectable levels of plasma LDL cholesterol levels
- 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)
- additional 2-fold increase in the rate of labeled LDL cholesterol clearance from plasma when lovastatin was added to the diet
Research Applications
This mouse can be used to support research in many areas including:
Cardiovascular Research
Atherosclerosis
Hypercholesterolemia
Hypocholesterolemia
Other (altered fat metabolism)
Other (altered lipoprotein profile)
Metabolism Research
Lipid Metabolism
Neurobiology Research
Alzheimer's Disease
Research Tools
Cardiovascular Research
| Allele Symbol | Pcsk9tm1Jdh | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Jay D Horton | ||
| Common Name(s) | Pcsk9-; | ||
| Mutation Made By | 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; 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 Protocols
Pcsk9tm1Jdh, SEP PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
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]
Pcsk9tm1Jdh related
Jonas 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]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]
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred together. Diet Information LabDiet® 5K52/5K67
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $155.70 Female or Male Homozygous for Pcsk9tm1Jdh *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $311.40 Homozygous for Pcsk9tm1Jdh x Homozygous for Pcsk9tm1Jdh
| 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 |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $202.50 Female or Male Homozygous for Pcsk9tm1Jdh *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $404.90 Homozygous for Pcsk9tm1Jdh x Homozygous for Pcsk9tm1Jdh
| 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. | ||
For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
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