Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N7F?+F4p   Donating Investigator Aldons Lusis,   University of California at Los Angeles

Description
Mice that are homozygous for this targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No paraoxonase activity is detected in blood plasma. Homozygous animals are extremely sensitive to the toxic effects of the chlorpyrifos and its active form, chlorpyrifos oxon, a potent cholinesterase inhibitor. When fed a high-fat, high-cholesterol diet, homozygous mice are more susceptible to atherosclerosis when compared to wildtype littermates. In vitro studies indicate that high-density lipoproteins derived from homozygous animals are unable to prevent low-density lipoprotein oxidation. This mutant mouse strain represents a model that may be useful in studies related to toxicology (particularly insecticide poisoning) and factors regulating susceptibility to atherosclerosis.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 1. The construct was electroporated into 129X1/SvJ-derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

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.

Pon1^tm1Lus/Pon1^tm1Lus

        involves: 129X1/SvJ * C57BL/6J

• cellular phenotype
• oxidative stress (MGI Ref ID J:82696)
  • increased oxidative stress in macrophages

View Research Applications

Research Applications

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

Pon1^tm1Lus related

Cardiovascular Research
Diet-Induced Atherosclerosis (Susceptible)

Research Tools
Sensorineural Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Pon1tm1Lus
Allele Name		targeted mutation 1, Aldons J Lusis
Allele Type		Targeted (knock-out)
Common Name(s)		PON10;
Mutation Made By		Aldons Lusis,   University of California at Los Angeles
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Pon1, paraoxonase 1
Chromosome		6
Gene Common Name(s)		ESA; PON; Pon; paraoxonase;
Molecular Note		Exon 1 is disrupted with a neomycin resistance gene via homlogous recombination. Plasma from homozygous mutant animals did not demonstrate paraoxonase activity and did not contain protein product as assayed by Western blot. [MGI Ref ID J:63392]

Genotyping

Genotyping Information

Genotyping Protocols

Pon1^tm1Lus, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Shih DM; Gu L; Xia YR; Navab M; Li WF; Hama S; Castellani LW; Furlong CE; Costa LG; Fogelman AM; Lusis AJ. 1998. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 394(6690):284-7. [PubMed: 9685159]  [MGI Ref ID J:63392]

Additional References

Shih DM; Xia YR; Wang XP; Miller E; Castellani LW; Subbanagounder G; Cheroutre H; Faull KF; Berliner JA; Witztum JL; Lusis AJ. 2000. Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem 275(23):17527-35. [PubMed: 10748217]  [MGI Ref ID J:62750]

Pon1^tm1Lus related

Furlong CE; Li WF; Costa LG; Richter RJ; Shih DM; Lusis AJ. 1998. Genetically determined susceptibility to organophosphorus insecticides and nerve agents: developing a mouse model for the human PON1 polymorphism. Neurotoxicology 19(4-5):645-50. [PubMed: 9745924]  [MGI Ref ID J:49974]

Rozenberg O; Rosenblat M; Coleman R; Shih DM; Aviram M. 2003. Paraoxonase (PON1) deficiency is associated with increased macrophage oxidative stress: studies in PON1-knockout mice. Free Radic Biol Med 34(6):774-84. [PubMed: 12633754]  [MGI Ref ID J:82696]

Rozenberg O; Shiner M; Aviram M; Hayek T. 2008. Paraoxonase 1 (PON1) attenuates diabetes development in mice through its antioxidative properties. Free Radic Biol Med 44(11):1951-9. [PubMed: 18358245]  [MGI Ref ID J:136069]

Shih DM; Xia YR; Wang XP; Miller E; Castellani LW; Subbanagounder G; Cheroutre H; Faull KF; Berliner JA; Witztum JL; Lusis AJ. 2000. Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem 275(23):17527-35. [PubMed: 10748217]  [MGI Ref ID J:62750]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129X1 background and has been backcrossed to C57BL/6J for at least seven generations (8/01).

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
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.

General Terms and Conditions

See Terms of Use

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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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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.

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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.