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+F6 (29-DEC-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 Information

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

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

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Pcsk9^tm1Jdh/Pcsk9^tm1Jdh

        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

View Research Applications

Research Applications

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

Allele Symbol		Pcsk9tm1Jdh
Allele Name		targeted mutation 1, Jay D Horton
Allele Type		Targeted (knock-out)
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

Genotyping Information

Genotyping Protocols

Ldlr ^tm1Her, Standard PCR
Pcsk9^tm1Jdh, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

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

Pcsk9^tm1Jdh 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]

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

Purchasing information

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

 

This strain is currently On Hold.
To register your interest in this strain go to the Strain Interest Form.

To request more information use the Customer Support Contact Form or call 1.800.422.6423 or 207.288.5845

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Supply Details

Standard Supply	This strain is currently on HOLD - Contact Customer Service for more information.
Supply Notes	7/14/09: This strain is on hold while we breed away for an unwanted mutation. This strain is included in the Induced Mutant Resource Colony collection.

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.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

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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Ordering and Purchasing Information

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Terms of Use

Terms of Use

General Terms and Conditions

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Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

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