Description

Strain Information

Former Names STOCK Ppidtm1.1Mmos/J    (Changed: 21-AUG-08 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Stanley Korsmeyer,   Dana-Farber Cancer Institute

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Brain architecture and cerebrovasculature are normal. No gene product (protein) is detected by immunoblot analysis of mitochondria isolated from liver tissue of mutant mice. Mitochondria from mutant mice have an increased capacity to retain calcium and fail to swell/rupture in response to CaCl₂, suggesting abnormal permeability transition pore (PTP) function. Mouse embryonic fibroblasts (MEFs) derived from mutant mice are less susceptible to oxidative stress induced in vitro by exposure to hydrogen peroxide than MEFs derived from wildtype mice. In a model of ischemic brain injury employing a middle cerebral artery occlusion protocol, mutant mice exhibited a reduced infarct volume (37% in heterozygotes, and 62% in homozygotes) when compared to wildtype mice. This mutant mouse strain may be useful in studies investigating oxidative stress- and ischemia–induced cell death.

Development
A targeting vector containing a loxP-flanked neomycin resistance gene cassette preceding exons 3-5 and a third loxP site downstream of exon 5 was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a pMC-Cre gene to delete the neo gene (resulting in loxP-flanked exons 3-5 [CypD^flox]) and then injected into C57BL/6 blastocysts. Chimeric mice were crossed to C57BL/6. The resulting heterozygotes were next crossed to FVB/N-Tg(EIIa-cre)C5379Lmgd/J (Stock No. 003314). Mice having been recombined such that exons 3-5 are replaced with a single loxP site (CypD^null) were intercrossed to generate mice homozygous for the deletion.

Control Information

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

Related Strains

Strains carrying other alleles of Ppif

005737

STOCK Ppiftm1Mmos/J

View Strains carrying other alleles of Ppif     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Ppif^tm1.1Mmos/Ppid⁺

        involves: 129X1/SvJ * FVB/NJ

• nervous system phenotype
• decreased cerebral infarction size (MGI Ref ID J:101149)
  • infarct volume induced by middle cerebral artery occlusion is reduced by 37% in heterozygotes relative to wild-type siblings
• homeostasis/metabolism phenotype
• decreased cerebral infarction size (MGI Ref ID J:101149)
  • infarct volume induced by middle cerebral artery occlusion is reduced by 37% in heterozygotes relative to wild-type siblings

Ppif^tm1.1Mmos/Ppif^tm1.1Mmos

        involves: 129X1/SvJ * FVB/NJ

• cellular phenotype
• abnormal mitochondrial physiology (MGI Ref ID J:101149)
  • cultured embryonic fibroblasts from homozygotes are less susceptible to H₂O₂ induced cell death but respond normally to etoposide, staurosporine, thapsigargin, tunicamycin, brefeldin A, tumor necrosis factor alpha and TNFSF10
  • 100uM CaCl₂ fails to induce mitochondiral swelling in mitochondria from homozygous liver
• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:101149)
  • normal brain and cerebrovasculature
• decreased cerebral infarction size (MGI Ref ID J:101149)
  • infarct volume induced by middle cerebral artery occlusion is reduced by 62% in homozygotes relative to wild-type siblings
• homeostasis/metabolism phenotype
• decreased cerebral infarction size (MGI Ref ID J:101149)
  • infarct volume induced by middle cerebral artery occlusion is reduced by 62% in homozygotes relative to wild-type siblings

View Research Applications

Research Applications

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

Cell Biology Research
Channel and Transporter Defects (calcium)

Metabolism Research
Free Radical Research

Research Tools
Apoptosis Research
Cell Biology Research
Metabolism Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ppiftm1.1Mmos
Allele Name		targeted mutation 1.1, Michael A Moskowitz
Allele Type		Targeted (knock-out)
Common Name(s)		CypDnull;
Mutation Made By		Stanley Korsmeyer,   Dana-Farber Cancer Institute
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Ppif, peptidylprolyl isomerase F (cyclophilin F)
Chromosome		14
Gene Common Name(s)		AW457192; CYP3; CyP-D; CyP-F; CypD; FLJ90798; MGC117207; MGC93084; PPIase; expressed sequence AW457192; mitochondrial Cyclophilin D;
Molecular Note		A targeting vector was designed to insert loxP sites around exons 3-5. Crossing with mice expressing cre in the germ line resulted in a null allele, as was demonstrated by immunoblot of liver samples. [MGI Ref ID J:101149]

Genotyping

Genotyping Information

Genotyping Protocols

Ppif^tm1.1Mmos, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Schinzel AC; Takeuchi O; Huang Z; Fisher JK; Zhou Z; Rubens J; Hetz C; Danial NN; Moskowitz MA; Korsmeyer SJ. 2005. Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia. Proc Natl Acad Sci U S A 102(34):12005-10. [PubMed: 16103352]  [MGI Ref ID J:101149]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.

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

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. 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
	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.

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
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

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.

Contact information

General inquiries

Contracts Administration

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.”

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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.