Exons 2-4 of the mouse Ltc4s gene were replaced with a neomycin cassette in this targeted mutant strain. Expression is significantly reduced. Homozygotes show reduced vascular permeabilities induced by zymosan and IgE crosslinking as well as reduced antigen-induced pulmonary inflammation and bleomycin-induced pulmonary fibrosis.
Yoshihide Kanaoka, Brigham and Women's Hospital
Ltc4s (leukotriene C4 synthase) is the terminal 5-lipoxygenase pathway enzyme that is responsible for the biosynthesis of cysteinyl leukotrienes. Cysteinyl leukotrienes are potent lipid mediators of tissue inflammation, particularly implicated in allergic and asthmatic diseases.
These mice carry a targeted knock-out of the mouse gene in which exons 2-4 were replaced with a neomycin cassette in reverse transcriptional orientation. LTC4S activity, assessed by conjugation of leukotriene (LT) A4 methyl ester with glutathione, is absent from tongue, spleen, and brain and more than 90% reduced in lung, stomach, and colon. An unstable mRNA transcript involving exon 5 and presumably the neomycin gene is detectable. Bone marrow-derived mast cells from the mice do not generate LTC4 in response to IgE-dependent activation.
Homozygous knock-out mice (which are viable, fertile, and without apparent abnormalities) show reduced vascular permeabilities induced by zymosan and IgE crosslinking. They also show reduced antigen-induced pulmonary inflammation and bleomycin-induced pulmonary fibrosis.
The phenotype of this C57BL/6N background strain is reported to be the same as that of the BALB/c genetic background line (see Stock No. 030959).
Exons 2-4 of the mouse Ltc4s gene, including Arg-51 in exon 2 and Tyr-93 in exon 4 (critical residues for gene activity), were replaced with a neomycin resistance cassette in reverse transcriptional orientation via homologous recombination in the AB2.2 129S7/SvEvBrd-Hprt1b-m2-derived embryonic stem (ES) cell line. This line was backcrossed to C57BL/6NCrl for 15 generations by the donating laboratory.
|Allele Name||targeted mutation 1, Bing K Lam|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Bing K Lam; Ltc4stm1Blam|
|Gene Symbol and Name||Ltc4s, leukotriene C4 synthase|
|Strain of Origin||129S7/SvEvBrd-Hprtb-m2|
|Molecular Note||A neomycin gene cassette replaced 289 nucleotides from intron 1 as well as exons 2 through 4 and 32 nucleotides from intron 4. Northern blot analysis of RNA from bone marrow macrophages confirmed the absence of normal transcripts. An exon 5 containing transcript was produced however. No leukotriene C4 was detectable.|
Homozygotes and heterozygotes are viable and fertile.
When using the LTC4S- mouse strain in a publication, please cite the originating article(s) and include JAX stock #030813 in your Materials and Methods section.
|Heterozygous for Ltc4s<tm1Blam>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
"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.
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.
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.
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.
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.