Overview

Also Known As:P-12LO-

These Alox12 knock-out mice exhibit a hyper-responsiveness to adenosine diphosphate (ADP) -induced platelet aggregation and may be is useful in studies of thromboembolism.

Genetic overview

Genetic Background	Generation

Alox12^tm1Fun

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Alox12	arachidonate 12-lipoxygenase

View Genetics

Research Applications

Dermatology Research
Hematological Research
Cardiovascular Research
Research Tools

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed 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 Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Alox12^tm1Fun

Allele Symbol: Alox12^tm1Fun

Allele Name	targeted mutation 1, Colin D Funk
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	12/15LO KO; P-12LO-
Gene Symbol and Name	Alox12, arachidonate 12-lipoxygenase
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	11
Molecular Note	A neomycin resistance cassette replaced exon 8. Western blot analysis did not detect the encoded protein in homozygous mutant platelets.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Alox12^tm1Fun related

Dermatology Research
- Other
  - Studies of transepidermal water loss
Hematological Research
- Platelet Defects
  - Alterations in platelet aggregation
Cardiovascular Research
- Vascular Defects
  - Thrombosis
Research Tools
- Hematological Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Alox12^tm1Fun/Alox12^tm1Fun
involves: 129S2/SvPas * C57BL/6

hematopoietic system phenotype

increased platelet aggregation
- mutant platelets exhibit increased sensitivity to ADP, manifested as a significant increase in slope and percent aggregation in ex vivo assays; 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
- Normal - platelet adhesion to various extracellular matrix proteins, including fibrinogen, collagen and fibronectin, is normal
- Normal - thrombin-, collagen-, U46619-, and arachidonic acid-induced aggregation responses are largely unaffected

integument phenotype

impaired skin barrier function
- homozygotes exhibit increased transepidermal water loss, without increased basal mitotic activity of epidermal cells, and normal recovery of the epidermal barrier after acetone disruption
- Normal - however, 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

mammalian phenotype

immune system phenotype
- Normal - homozygotes exhibit a normal arachidonic acid-induced ear inflammatory response, as measured by plasma leakage and edema formation

homeostasis/metabolism phenotype

altered susceptibility to induced thrombosis
- 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

impaired skin barrier function
- homozygotes exhibit increased transepidermal water loss, without increased basal mitotic activity of epidermal cells, and normal recovery of the epidermal barrier after acetone disruption
- Normal - however, 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

increased platelet aggregation
- mutant platelets exhibit increased sensitivity to ADP, manifested as a significant increase in slope and percent aggregation in ex vivo assays; 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
- Normal - platelet adhesion to various extracellular matrix proteins, including fibrinogen, collagen and fibronectin, is normal
- Normal - thrombin-, collagen-, U46619-, and arachidonic acid-induced aggregation responses are largely unaffected

increased susceptibility to induced thrombosis
- 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)
- Normal - however, no differences in mortality are observed with arachidonic acid-induced thrombosis at 30 mg/kg and 100 mg/kg

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):161-5PubMed: 11146221 MGI: J:67133

Additional - Alox12^tm1Fun related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Alox12
- Genotyping resources and troubleshooting
Breeding Considerations

This 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
- Additional Breeding and Husbandry Support
Citation
When using the P-12LO- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004042 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Alox12<tm1Fun>

Related Products and Services

Frozen Mouse Embryo	B6.129S2-Alox12<tm1Fun>/J	$2595.00
Frozen Mouse Embryo	B6.129S2-Alox12<tm1Fun>/J	$2595.00
Frozen Mouse Embryo	B6.129S2-Alox12<tm1Fun>/J	$3373.50
Frozen Mouse Embryo	B6.129S2-Alox12<tm1Fun>/J	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (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. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, 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 JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES 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 JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or SERVICES by JACKSON.

Also Known As:P-12LO-

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Alox12tm1Fun

Allele Symbol: Alox12tm1Fun

Disease Terms

Research Areas By Phenotype

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

Genotype: Alox12tm1Fun related

Mammalian Phenotype Terms by Genotype

Genotype: Alox12tm1Fun/Alox12tm1Funinvolves: 129S2/SvPas * C57BL/6

hematopoietic system phenotype

integument phenotype

mammalian phenotype

homeostasis/metabolism phenotype

References

Additional References

Additional - Alox12tm1Fun related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Alox12^tm1Fun

Allele Symbol: Alox12^tm1Fun

Genotype: Alox12^tm1Fun related

Genotype: Alox12^tm1Fun/Alox12^tm1Fun
involves: 129S2/SvPas * C57BL/6

Additional - Alox12^tm1Fun related