Description

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Beverly Koller,   Univ. of North Carolina at Chapel Hill

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. No gene product (mRNA) is detected in isolated bone marrow cells. No final product of the reaction catalyzed by the targeted gene product enzyme is detected in peritoneal lavage fluids from mice with experimental peritonitis. Acute inflammatory reaction induced by topical arachidonic acid application to the inner surface of the ear produces a reduced vascular and cellular response in homozygous mice. Edema formation, as assessed by weight of ear biopsies, and protein extravasation into the inflamed tissue is diminished. Neutrophil infiltrate and myeloperoxidase activity is significantly decreased. Inflammatory response to zymosan-A induced peritonitis is characterized by reduced polymorphonuclear neutrophil infiltration into the peritoneal cavity. Homozygous mice are resistant to platelet-activating factor induced systemic shock. This mutant mouse strain may be useful in studies examining the role of LTB4 in inflammatory responses.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the coding sequence at bp 738 and remove 114 bp of coding sequence (bases 739-853). The construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to 129 mice (mixed 129P2;129S6).

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Lta4h^tm1Bhk/Lta4h^tm1Bhk

        involves: 129P2/OlaHsd * 129S/SvEv

• immune system phenotype
• decreased acute inflammation (MGI Ref ID J:58985)
  • skin reactions reduced
  • less protein leakage from the vasculature in skin reactions but not peritonitis
  • reduced influx of polymorphonuclear leukocytes into peritoneal cavity
• decreased susceptibility to type I hypersensitivity reaction (MGI Ref ID J:58985)
  • reduced anaphylaxis induced by platelet activating factor but not by other methods

View Research Applications

Research Applications

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

Lta4h^tm1Bhk related

Immunology and Inflammation Research
Inflammation

Metabolism Research
Enzyme Deficiency

Genes & Alleles

Gene & Allele Information

Allele Symbol		Lta4htm1Bhk
Allele Name		targeted mutation 1, Beverly H Koller
Allele Type		Targeted (knock-out)
Common Name(s)		LtA4 hydrolase<->;
Mutation Made By		Beverly Koller,   Univ. of North Carolina at Chapel Hill
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14TG2a
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Lta4h, leukotriene A4 hydrolase
Chromosome		10
Gene Common Name(s)		LTA4 hydrodase;
Molecular Note		A neomycin selection cassette replaced 114 base pairs of coding sequence. Northern blot analysis of total RNA showed an absence of transcript in bone marrow and bone marrow mast cells, both obtained from homozygous mutant mice. [MGI Ref ID J:58985]

Genotyping

Genotyping Information

Genotyping Protocols

Lta4h^tm1Bhk, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Byrum RS; Goulet JL; Snouwaert JN; Griffiths RJ; Koller BH. 1999. Determination of the contribution of cysteinyl leukotrienes and leukotriene B4 in acute inflammatory responses using 5-lipoxygenase- and leukotriene A4 hydrolase-deficient mice. J Immunol 163(12):6810-9. [PubMed: 10586081]  [MGI Ref ID J:58985]

Additional References

Lta4h^tm1Bhk related

Chen M; Lam BK; Kanaoka Y; Nigrovic PA; Audoly LP; Austen KF; Lee DM. 2006. Neutrophil-derived leukotriene B4 is required for inflammatory arthritis. J Exp Med 203(4):837-42. [PubMed: 16567388]  [MGI Ref ID J:123751]

Miyahara N; Ohnishi H; Matsuda H; Miyahara S; Takeda K; Koya T; Matsubara S; Okamoto M; Dakhama A; Haribabu B; Gelfand EW. 2008. Leukotriene B4 receptor 1 expression on dendritic cells is required for the development of Th2 responses and allergen-induced airway hyperresponsiveness. J Immunol 181(2):1170-8. [PubMed: 18606670]  [MGI Ref ID J:137467]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain originated on a 129P2 background and was backcrossed once on the 129S6 background before being made homozygous.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-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.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, and by its licensees and distributors.

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