Strain Name:

B6.129S2-Alox12tm1Fun/J

Stock Number:

004042

Availability:

Repository-Cryopreserved

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
GenerationN8F?+5pN1

Description
Mice that are homozygous null for the Alox12 gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Alox12 protein product or enzyme activity is detected in platelets derived from homozygous null animals. Platelets exhibit a hyperresponsiveness to ADP-induced aggregation. Studies examining basal transepidermal water loss indicate that null animals exhibit greater water loss through the skin when compared to control animals.

Development
A targeting vector containing a neomycin cassette was used to disrupt exon 8. The construct was electroporated into 129S2/SvPas-derived D3H embryonic stem cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric animals were obtained.

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.

Alox12tm1Fun/Alox12tm1Fun

        involves: 129S2/SvPas * C57BL/6
  • homeostasis/metabolism phenotype
  • abnormal platelet physiology (MGI Ref ID J:46896)
    • homozygotes display normal platelet adhesion to various extracellular matrix proteins including fibrinogen, collagen, and fibronectin; in addition, thrombin, collagen, U46619, and arachidonic acid-induced aggregation responses are largely unaffected
    • however, mutant platelets exhibit increased sensitivity to ADP, manifested as a significant increase in slope and percent aggregation in ex vivo assays
    • notably, platelet hyperresponsiveness to ADP is not secondary to thromboxane synthesis, PKC activity, or dense granule release and can be attenuated by the addition of 12-(S)-hydroperoxyeicosatetraenoic acid to platelet-rich plasma
  • impaired skin barrier function (MGI Ref ID J:55741)
    • homozygotes exhibit increased transepidermal water loss, without increased basal mitotic activity of epidermal cells, and normal recovery of the epidermal barrier after acetone disruption
    • notably, the mutant epidermis appears structurally normal, with no detectable differences in number or appearance of lamellar bodies and no changes in the content of major fatty acids
  • thrombosis (MGI Ref ID J:46896)
    • homozygotes are more sensitive to thrombosis elicited by i.v. ADP injection: 87.5% of mutants (vs only 20% of wild-type) exhibit thrombolytic death at an ADP dose of 0.035 mg/g (body weight)
    • in contrast, no differences in mortality with arachidonic acid-induced thrombosis are observed at 30 mg/kg and 100 mg/kg
  • hematopoietic system phenotype
  • abnormal platelet physiology (MGI Ref ID J:46896)
    • homozygotes display normal platelet adhesion to various extracellular matrix proteins including fibrinogen, collagen, and fibronectin; in addition, thrombin, collagen, U46619, and arachidonic acid-induced aggregation responses are largely unaffected
    • however, mutant platelets exhibit increased sensitivity to ADP, manifested as a significant increase in slope and percent aggregation in ex vivo assays
    • notably, platelet hyperresponsiveness to ADP is not secondary to thromboxane synthesis, PKC activity, or dense granule release and can be attenuated by the addition of 12-(S)-hydroperoxyeicosatetraenoic acid to platelet-rich plasma
  • skin/coat/nails phenotype
  • impaired skin barrier function (MGI Ref ID J:55741)
    • homozygotes exhibit increased transepidermal water loss, without increased basal mitotic activity of epidermal cells, and normal recovery of the epidermal barrier after acetone disruption
    • notably, the mutant epidermis appears structurally normal, with no detectable differences in number or appearance of lamellar bodies and no changes in the content of major fatty acids
  • immune system phenotype
  • *normal* immune system phenotype (MGI Ref ID J:55741)
    • homozygotes exhibit a normal arachidonic acid-induced ear inflammatory response, as measured by plasma leakage and edema formation
View Research Applications

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

Alox12tm1Fun related

Cardiovascular Research
Vascular Defects (Thrombosis)

Dermatology Research
Other (Studies of transepidermal water loss)

Hematological Research
Platelet Defects (Alterations in platelet aggregation)

Research Tools
Hematological Research

Genes & Alleles

Gene & Allele Information

Allele Symbol Alox12tm1Fun
Allele Name targeted mutation 1, Colin Funk
Allele Type Targeted (knock-out)
Common Name(s) P-12LO-;
Strain of Origin129S2/SvPas
ES Cell Line NameD3H
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Alox12, arachidonate 12-lipoxygenase
Chromosome 11
Gene Common Name(s) 12-LOX; 12S-LOX; 9930022G08Rik; Alox12p; LOG12; MGC187960; P-12LO; RIKEN cDNA 9930022G08 gene; arachidonate 12-lipoxygenase, platelet;
Molecular Note Insertion of a neomycin resistance cassette deleted exon 8 of the Alox12 gene. Western blot analysis did not detect protein in homozygous mutant platelets. [MGI Ref ID J:46896]

Genotyping

Genotyping Information

Genotyping Protocols

Alox12tm1Fun, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Virmani J; Johnson EN; Klein-Szanto AJ; Funk CD. 2001. Role of 'platelet-type' 12-lipoxygenase in skin carcinogenesis. Cancer Lett 162(2):161-5. [PubMed: 11146221]  [MGI Ref ID J:67133]

Alox12tm1Fun related

Bleich D; Chen S; Zipser B; Sun D; Funk CD; Nadler JL. 1999. Resistance to type 1 diabetes induction in 12-lipoxygenase knockout mice. J Clin Invest 103(10):1431-6. [PubMed: 10330425]  [MGI Ref ID J:55050]

Gabel SA; London RE; Funk CD; Steenbergen C; Murphy E. 2001. Leukocyte-type 12-lipoxygenase-deficient mice show impaired ischemic preconditioning-induced cardioprotection. Am J Physiol Heart Circ Physiol 280(5):H1963-9. [PubMed: 11299195]  [MGI Ref ID J:69296]

Gubitosi-Klug RA; Talahalli R; Du Y; Nadler JL; Kern TS. 2008. 5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy. Diabetes 57(5):1387-93. [PubMed: 18346986]  [MGI Ref ID J:136092]

Johnson EN; Brass LF; Funk CD. 1998. Increased platelet sensitivity to ADP in mice lacking platelet-type 12-lipoxygenase. Proc Natl Acad Sci U S A 95(6):3100-5. [PubMed: 9501222]  [MGI Ref ID J:46896]

Johnson EN; Nanney LB; Virmani J; Lawson JA; Funk CD. 1999. Basal transepidermal water loss is increased in platelet-type 12-lipoxygenase deficient mice. J Invest Dermatol 112(6):861-5. [PubMed: 10383730]  [MGI Ref ID J:55741]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryThis strain originated on a B6;129S2 background and has been backcrossed to C57BL/6J for eight generations before being made homozygous.Coat color expected from breeding:Black
Diet Information LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
*Price(s) in US dollars ($)

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
*Price(s) in US dollars ($)

Additional Supply Details

Supply Details

Standard SupplyRepository-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.

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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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General Terms and Conditions


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