Strain Name:

B6.129X-Ephx2tm1Gonz/J

Stock Number:

004165

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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

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHomozygote x Homozygote         (Female x Male)   19-AUG-06
Specieslaboratory mouse
 
Donating InvestigatorDr. Frank Gonzalez,   National Institutes of Health

Description
Mice homozygous for the targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Ephx2 gene product (mRNA or protein) is detected. Systolic blood pressure is minimally effected in homozygous females but males exhibit markedly lower blood pressure. Both sexes also display an altered arachidonic acid metabolism; renal formation of dihydroxyeicosatrienoic acid is significantly diminished. This mutant mouse strain represents a model that may be useful in studies related to blood pressure regulation.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt a region of the Ephx2 gene encoding exon 1. The construct was electroporated into 129X1/SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting male chimeric animals were mated to C57BL/6 mice.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Hypercholesterolemia, Familial   (EPHX2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Ephx2tm1Gonz/Ephx2tm1Gonz

        involves: 129X1/SvJ * C57BL/6
  • cardiovascular system phenotype
  • decreased systemic arterial systolic blood pressure
    • male homozygotes exhibit reduced systolic blood pressure both in the absence and presence of dietary salt loading compared with sex matched, wild-type mice   (MGI Ref ID J:71007)
    • in contrast, female homozygotes show minimal differences in systolic blood pressure relative to wild-type mice   (MGI Ref ID J:71007)
    • both mutant and wild-type female mice exhibit significantly lower systolic blood pressure than male wild-type mice   (MGI Ref ID J:71007)
  • homeostasis/metabolism phenotype
  • abnormal metabolism
    • homozygotes of both sexes exhibit impaired hepatic and renal arachidonic acid metabolism   (MGI Ref ID J:71007)
    • homozygotes display a 58-fold greater ratio of epoxyeicosatrienoic/dihydroxyeicosatrienoic acid (EETs/DHETs) specific activity in hepatic S-9 fractions relative to wild-type mice   (MGI Ref ID J:71007)
    • also, homozygotes show a significant reduction in DHETs formation by kidney S-9 fractions, regardless of sex and diet   (MGI Ref ID J:71007)
View Research Applications

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

Ephx2tm1Gonz related

Cardiovascular Research
Hypotension

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ephx2tm1Gonz
Allele Name targeted mutation 1, Frank Gonzalez
Allele Type Targeted (knock-out)
Common Name(s) sEH-null; sEH-;
Mutation Made ByDr. Frank Gonzalez,   National Institutes of Health
Strain of Origin129X1/SvJ
Gene Symbol and Name Ephx2, epoxide hydrolase 2, cytoplasmic
Chromosome 14
Gene Common Name(s) AW106936; CEH; Eph2; SEH; epoxide hydrolase 2, soluble; expressed sequence AW106936; sEP;
Molecular Note Insertion of a neomycin resistance cassette into the translation initiation site in the first exon. Northern analysis did not detect transcript in liver from homozygous mutant mice. Immunoblot analysis did not detect protein in cytosolic fractions of liver from homozygous mutant mice. [MGI Ref ID J:71007]

Genotyping

Genotyping Information

Genotyping Protocols

Ephx2tm1Gonz, Melt Curve Analysis
Ephx2tm1Gonz, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Sinal CJ; Miyata M; Tohkin M; Nagata K; Bend JR; Gonzalez FJ. 2000. Targeted disruption of soluble epoxide hydrolase reveals a role in blood pressure regulation. J Biol Chem 275(51):40504-10. [PubMed: 11001943]  [MGI Ref ID J:71007]

Additional References

Ephx2tm1Gonz related

Ai D; Pang W; Li N; Xu M; Jones PD; Yang J; Zhang Y; Chiamvimonvat N; Shyy JY; Hammock BD; Zhu Y. 2009. Soluble epoxide hydrolase plays an essential role in angiotensin II-induced cardiac hypertrophy. Proc Natl Acad Sci U S A 106(2):564-9. [PubMed: 19126686]  [MGI Ref ID J:143868]

Bettaieb A; Nagata N; AbouBechara D; Chahed S; Morisseau C; Hammock BD; Haj FG. 2013. Soluble epoxide hydrolase deficiency or inhibition attenuates diet-induced endoplasmic reticulum stress in liver and adipose tissue. J Biol Chem 288(20):14189-99. [PubMed: 23576437]  [MGI Ref ID J:199627]

Chen G; Xu R; Wang Y; Wang P; Zhao G; Xu X; Gruzdev A; Zeldin DC; Wang DW. 2012. Genetic disruption of soluble epoxide hydrolase is protective against streptozotocin-induced diabetic nephropathy. Am J Physiol Endocrinol Metab 303(5):E563-75. [PubMed: 22739108]  [MGI Ref ID J:189529]

Cronin A; Decker M; Arand M. 2011. Mammalian soluble epoxide hydrolase is identical to liver hepoxilin hydrolase. J Lipid Res 52(4):712-9. [PubMed: 21217101]  [MGI Ref ID J:170657]

Elmarakby AA; Faulkner J; Al-Shabrawey M; Wang MH; Maddipati KR; Imig JD. 2011. Deletion of soluble epoxide hydrolase gene improves renal endothelial function and reduces renal inflammation and injury in streptozotocin-induced type 1 diabetes. Am J Physiol Regul Integr Comp Physiol 301(5):R1307-17. [PubMed: 21832210]  [MGI Ref ID J:178808]

Enayetallah AE; Luria A; Luo B; Tsai HJ; Sura P; Hammock BD; Grant DF. 2008. Opposite regulation of cholesterol levels by the phosphatase and hydrolase domains of soluble epoxide hydrolase. J Biol Chem 283(52):36592-8. [PubMed: 18974052]  [MGI Ref ID J:143932]

Fairbanks SL; Young JM; Nelson JW; Davis CM; Koerner IP; Alkayed NJ. 2012. Mechanism of the sex difference in neuronal ischemic cell death. Neuroscience 219:183-91. [PubMed: 22641086]  [MGI Ref ID J:192422]

Fromel T; Jungblut B; Hu J; Trouvain C; Barbosa-Sicard E; Popp R; Liebner S; Dimmeler S; Hammock BD; Fleming I. 2012. Soluble epoxide hydrolase regulates hematopoietic progenitor cell function via generation of fatty acid diols. Proc Natl Acad Sci U S A 109(25):9995-10000. [PubMed: 22665795]  [MGI Ref ID J:185508]

Hercule HC; Schunck WH; Gross V; Seringer J; Leung FP; Weldon SM; da Costa Goncalves ACh; Huang Y; Luft FC; Gollasch M. 2009. Interaction between P450 eicosanoids and nitric oxide in the control of arterial tone in mice. Arterioscler Thromb Vasc Biol 29(1):54-60. [PubMed: 18927469]  [MGI Ref ID J:159789]

Hou HH; Hammock BD; Su KH; Morisseau C; Kou YR; Imaoka S; Oguro A; Shyue SK; Zhao JF; Lee TS. 2012. N-terminal domain of soluble epoxide hydrolase negatively regulates the VEGF-mediated activation of endothelial nitric oxide synthase. Cardiovasc Res 93(1):120-9. [PubMed: 22072631]  [MGI Ref ID J:194872]

Katragadda D; Batchu SN; Cho WJ; Chaudhary KR; Falck JR; Seubert JM. 2009. Epoxyeicosatrienoic acids limit damage to mitochondrial function following stress in cardiac cells. J Mol Cell Cardiol 46(6):867-75. [PubMed: 19285984]  [MGI Ref ID J:157145]

Keseru B; Barbosa-Sicard E; Popp R; Fisslthaler B; Dietrich A; Gudermann T; Hammock BD; Falck JR; Weissmann N; Busse R; Fleming I. 2008. Epoxyeicosatrienoic acids and the soluble epoxide hydrolase are determinants of pulmonary artery pressure and the acute hypoxic pulmonary vasoconstrictor response. FASEB J 22(12):4306-15. [PubMed: 18725458]  [MGI Ref ID J:146045]

Keseru B; Barbosa-Sicard E; Schermuly RT; Tanaka H; Hammock BD; Weissmann N; Fisslthaler B; Fleming I. 2010. Hypoxia-induced pulmonary hypertension: comparison of soluble epoxide hydrolase deletion vs. inhibition. Cardiovasc Res 85(1):232-40. [PubMed: 19679679]  [MGI Ref ID J:172557]

Liu Y; Dang H; Li D; Pang W; Hammock BD; Zhu Y. 2012. Inhibition of soluble epoxide hydrolase attenuates high-fat-diet-induced hepatic steatosis by reduced systemic inflammatory status in mice. PLoS One 7(6):e39165. [PubMed: 22720061]  [MGI Ref ID J:187826]

Luria A; Bettaieb A; Xi Y; Shieh GJ; Liu HC; Inoue H; Tsai HJ; Imig JD; Haj FG; Hammock BD. 2011. Soluble epoxide hydrolase deficiency alters pancreatic islet size and improves glucose homeostasis in a model of insulin resistance. Proc Natl Acad Sci U S A 108(22):9038-43. [PubMed: 21571638]  [MGI Ref ID J:173238]

Luria A; Morisseau C; Tsai HJ; Yang J; Inceoglu B; De Taeye B; Watkins SM; Wiest MM; German JB; Hammock BD. 2009. Alteration in plasma testosterone levels in male mice lacking soluble epoxide hydrolase. Am J Physiol Endocrinol Metab 297(2):E375-83. [PubMed: 19458064]  [MGI Ref ID J:151245]

Luria A; Weldon SM; Kabcenell AK; Ingraham RH; Matera D; Jiang H; Gill R; Morisseau C; Newman JW; Hammock BD. 2007. Compensatory mechanism for homeostatic blood pressure regulation in Ephx2 gene-disrupted mice. J Biol Chem 282(5):2891-8. [PubMed: 17135253]  [MGI Ref ID J:120290]

Merkel MJ; Liu L; Cao Z; Packwood W; Young J; Alkayed NJ; Van Winkle DM. 2010. Inhibition of soluble epoxide hydrolase preserves cardiomyocytes: role of STAT3 signaling. Am J Physiol Heart Circ Physiol 298(2):H679-87. [PubMed: 20008276]  [MGI Ref ID J:158438]

Motoki A; Merkel MJ; Packwood WH; Cao Z; Liu L; Iliff J; Alkayed NJ; Van Winkle DM. 2008. Soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo. Am J Physiol Heart Circ Physiol 295(5):H2128-34. [PubMed: 18835921]  [MGI Ref ID J:141436]

Revermann M; Schloss M; Barbosa-Sicard E; Mieth A; Liebner S; Morisseau C; Geisslinger G; Schermuly RT; Fleming I; Hammock BD; Brandes RP. 2010. Soluble epoxide hydrolase deficiency attenuates neointima formation in the femoral cuff model of hyperlipidemic mice. Arterioscler Thromb Vasc Biol 30(5):909-14. [PubMed: 20224052]  [MGI Ref ID J:175818]

Seubert JM; Sinal CJ; Graves J; DeGraff LM; Bradbury JA; Lee CR; Goralski K; Carey MA; Luria A; Newman JW; Hammock BD; Falck JR; Roberts H; Rockman HA; Murphy E; Zeldin DC. 2006. Role of soluble epoxide hydrolase in postischemic recovery of heart contractile function. Circ Res 99(4):442-50. [PubMed: 16857962]  [MGI Ref ID J:124860]

Simpkins AN; Rudic RD; Roy S; Tsai HJ; Hammock BD; Imig JD. 2010. Soluble epoxide hydrolase inhibition modulates vascular remodeling. Am J Physiol Heart Circ Physiol 298(3):H795-806. [PubMed: 20035028]  [MGI Ref ID J:158430]

Zhang W; Otsuka T; Sugo N; Ardeshiri A; Alhadid YK; Iliff JJ; DeBarber AE; Koop DR; Alkayed NJ. 2008. Soluble epoxide hydrolase gene deletion is protective against experimental cerebral ischemia. Stroke 39(7):2073-8. [PubMed: 18369166]  [MGI Ref ID J:141718]

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, G200.

Colony Maintenance

Breeding & HusbandryThis strain originated on a B6;129X1 background and has been backcrossed to C57BL/6 for at least five generations.
Mating SystemHomozygote x Homozygote         (Female x Male)   19-AUG-06

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2450.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $1600.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3185.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $2080.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   000664 C57BL/6J
 
  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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