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)   02-APR-10 Species laboratory mouse Generation F?+F5 (29-JUN-11) Generation Definitions   Donating Investigator Jeffery D. Molkentin,   Children's Hospital Medical Center

Description
Mitochondria isolated from the livers, hearts, and brains of homozygous targeted mutant mice are resistant to swelling and permeability transition in vitro. Hepatocytes and fibroblasts are largely protected from Ca²⁺-overload and oxidative stress-induced cell death. Mice are protected from ischaemia/reperfusion-induced cell death in vivo. This strain may be useful in studies of mitochondrial-driven cell death.

Development
The first three coding exons were replaced with a neomycin resistance cassette. A 129-dervived emabryonic stem (ES) cell line was used to create the mutation. Chimeras were crossed to C57BL/6 and the strain was maintained on a mixed C57BL/6 and 129 genetic background by the donating laboratory.

Control Information

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

Related Strains

Strains carrying other alleles of Ppif

005740	STOCK Ppiftm1.1Mmos/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

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

Ppif^tm1Jmol/Ppif^tm1Jmol

        involves: 129/Sv

• cellular phenotype
• abnormal mitochondrial physiology
  • resistant to swelling and permeability transition induced by lower calcium ion levels   (MGI Ref ID J:97660)
  • greater capacity for calcium uptake   (MGI Ref ID J:97660)
• cardiovascular system phenotype
• decreased myocardial infarction size
  • 40% reduction in infarction area when subjected to cardiac ischemia/reperfusion injury   (MGI Ref ID J:97660)
• homeostasis/metabolism phenotype
• decreased myocardial infarction size
  • 40% reduction in infarction area when subjected to cardiac ischemia/reperfusion injury   (MGI Ref ID J:97660)

View Research Applications

Research Applications

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

Apoptosis Research

Cell Biology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ppiftm1Jmol
Allele Name		targeted mutation 1, Jeffery D Molkentin
Allele Type		Targeted (knock-out)
Common Name(s)		Ppif-;
Mutation Made By		Jeffery Molkentin,   Children's Hospital Medical Center
Strain of Origin		129
ES Cell Line Strain		129
Gene Symbol and Name		Ppif, peptidylprolyl isomerase F (cyclophilin F)
Chromosome		14
Gene Common Name(s)		AW457192; CYP3; CyP-D; CyP-F; CyP-M; CypD; PPIase; expressed sequence AW457192; mitochondrial Cyclophilin D;
Molecular Note		A neomycin resistance gene replaced the first three coding exons. Western blot of cardiac protein extracts from mutants demonstrated the lack of protein. [MGI Ref ID J:97660]

Genotyping

Genotyping Information

Genotyping Protocols

Ppif^tm1Jmol SEP PCR, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Baines CP; Kaiser RA; Purcell NH; Blair NS; Osinska H; Hambleton MA; Brunskill EW; Sayen MR; Gottlieb RA; Dorn GW; Robbins J; Molkentin JD. 2005. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434(7033):658-62. [PubMed: 15800627]  [MGI Ref ID J:97660]

Additional References

Ppif^tm1Jmol related

Baines CP; Kaiser RA; Sheiko T; Craigen WJ; Molkentin JD. 2007. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol 9(5):550-5. [PubMed: 17417626]  [MGI Ref ID J:129616]

Ch'en IL; Tsau JS; Molkentin JD; Komatsu M; Hedrick SM. 2011. Mechanisms of necroptosis in T cells. J Exp Med 208(4):633-41. [PubMed: 21402742]  [MGI Ref ID J:177328]

Chen Y; Lewis W; Diwan A; Cheng EH; Matkovich SJ; Dorn GW 2nd. 2010. Dual autonomous mitochondrial cell death pathways are activated by Nix/BNip3L and induce cardiomyopathy. Proc Natl Acad Sci U S A 107(20):9035-42. [PubMed: 20418503]  [MGI Ref ID J:160306]

Devalaraja-Narashimha K; Diener AM; Padanilam BJ. 2011. Cyclophilin D deficiency prevents diet-induced obesity in mice. FEBS Lett 585(4):677-82. [PubMed: 21276794]  [MGI Ref ID J:169090]

Du H; Guo L; Fang F; Chen D; Sosunov AA; McKhann GM; Yan Y; Wang C; Zhang H; Molkentin JD; Gunn-Moore FJ; Vonsattel JP; Arancio O; Chen JX; Yan SD. 2008. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med 14(10):1097-105. [PubMed: 18806802]  [MGI Ref ID J:142839]

Du H; Guo L; Zhang W; Rydzewska M; Yan S. 2011. Cyclophilin D deficiency improves mitochondrial function and learning/memory in aging Alzheimer disease mouse model. Neurobiol Aging 32(3):398-406. [PubMed: 19362755]  [MGI Ref ID J:173741]

Elrod JW; Wong R; Mishra S; Vagnozzi RJ; Sakthievel B; Goonasekera SA; Karch J; Gabel S; Farber J; Force T; Brown JH; Murphy E; Molkentin JD. 2010. Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice. J Clin Invest 120(10):3680-7. [PubMed: 20890047]  [MGI Ref ID J:165325]

Hausenloy DJ; Lim SY; Ong SG; Davidson SM; Yellon DM. 2010. Mitochondrial cyclophilin-D as a critical mediator of ischaemic preconditioning. Cardiovasc Res 88(1):67-74. [PubMed: 20400621]  [MGI Ref ID J:183212]

Jobe SM; Wilson KM; Leo L; Raimondi A; Molkentin JD; Lentz SR; Di Paola J. 2008. Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis. Blood 111(3):1257-65. [PubMed: 17989312]  [MGI Ref ID J:130683]

Li V; Brustovetsky T; Brustovetsky N. 2009. Role of cyclophilin D-dependent mitochondrial permeability transition in glutamate-induced calcium deregulation and excitotoxic neuronal death. Exp Neurol 218(2):171-82. [PubMed: 19236863]  [MGI Ref ID J:151279]

Millay DP; Sargent MA; Osinska H; Baines CP; Barton ER; Vuagniaux G; Sweeney HL; Robbins J; Molkentin JD. 2008. Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy. Nat Med 14(4):442-7. [PubMed: 18345011]  [MGI Ref ID J:133679]

Naga KK; Sullivan PG; Geddes JW. 2007. High cyclophilin D content of synaptic mitochondria results in increased vulnerability to permeability transition. J Neurosci 27(28):7469-75. [PubMed: 17626207]  [MGI Ref ID J:122991]

Nakayama H; Chen X; Baines CP; Klevitsky R; Zhang X; Zhang H; Jaleel N; Chua BH; Hewett TE; Robbins J; Houser SR; Molkentin JD. 2007. Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J Clin Invest 117(9):2431-44. [PubMed: 17694179]  [MGI Ref ID J:127481]

Whelan RS; Konstantinidis K; Wei AC; Chen Y; Reyna DE; Jha S; Yang Y; Calvert JW; Lindsten T; Thompson CB; Crow MT; Gavathiotis E; Dorn GW 2nd; O'Rourke B; Kitsis RN. 2012. Bax regulates primary necrosis through mitochondrial dynamics. Proc Natl Acad Sci U S A 109(17):6566-71. [PubMed: 22493254]  [MGI Ref ID J:183839]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, homozygotes or heterozygotes may be bred. Homozygotes are smaller than wildtype mice and are prone to obesity as they age.
Mating System	Homozygote x Homozygote         (Female x Male)   02-APR-10
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

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'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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