Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names STOCK Ppidtm1.1Mmos/J    (Changed: 21-AUG-08 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. 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

009071	B6;129-Ppiftm1Jmol/J
005737	STOCK Ppiftm1Mmos/J

View Strains carrying other alleles of Ppif     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Ppif^tm1.1Mmos/Ppif⁺

        involves: 129X1/SvJ * FVB/NJ

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

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

        involves: 129X1/SvJ * FVB/NJ

• cellular phenotype
• abnormal mitochondrial physiology
  • 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   (MGI Ref ID J:101149)
  • 100uM CaCl₂ fails to induce mitochondiral swelling in mitochondria from homozygous liver   (MGI Ref ID J:101149)
• nervous system phenotype
• *normal* nervous system phenotype
  • normal brain and cerebrovasculature   (MGI Ref ID J:101149)
• • decreased cerebral infarction size
    • infarct volume induced by middle cerebral artery occlusion is reduced by 62% in homozygotes relative to wild-type siblings   (MGI Ref ID J:101149)
• homeostasis/metabolism phenotype
• decreased cerebral infarction size
  • infarct volume induced by middle cerebral artery occlusion is reduced by 62% in homozygotes relative to wild-type siblings   (MGI Ref ID J:101149)

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 provided by MGI

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; 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, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Additional References

Ppif^tm1.1Mmos related

Devalaraja-Narashimha K; Diener AM; Padanilam BJ. 2009. Cyclophilin D gene ablation protects mice from ischemic renal injury. Am J Physiol Renal Physiol 297(3):F749-59. [PubMed: 19553348]  [MGI Ref ID J:152200]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

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

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	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.

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