Mice homozygous for Alox5tm1Fun are in general selectively resistant to inflammatory insults. Because Leukotrienes are derived from 5-lipoxygenase-catalysed oxygenation of arachidonic acid in granulocytes, macrophages and mast cells, this strain may be useful in studying roles of leukotrienes in the pathophysiology of select inflammatory states
Colin D. Funk, Queen's University
Mice homozygous for the Alox5tm1Fun targeted mutation are viable and fertile. In general, homozygous mutant mice are selectively resistant to inflammatory insults. They are resistant to the lethal effects of platelet activating factor but reaction to endotoxin shock is normal. Phorbol ester induced inflammation is normal but arachidonic acid induced inflammation is reduced.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the Alox5 gene. The construct was electroporated into 129S2/SvPas-derived D3H embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The donating investigator reports that the resulting chimeric male animals were backcrossed to C57BL/6J females (see SNP note below).
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Colin D Funk|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||5-LO KO; 5-LO-; 5LO-; 5-LOX K/O; 5-LOX-; 5LX-|
|Gene Symbol and Name||Alox5, arachidonate 5-lipoxygenase|
|Strain of Origin||129S2/SvPas|
|Molecular Note||Insertion of a neomycin resistance cassette into exon 6 disrupted the Alox5 gene. RT-PCR studies did not detect transcript in resident peritoneal macrophages of homozygous mutant mice. Western blot analysis of resident peritoneal macrophages of homozygous mutant mice did not detect ALOX5.|
|Mutations Made By|| |
Colin Funk, Queen's University
This strain originated on a B6;129S2 background and has been backcrossed to C57BL/6J for at least nine generations(8/21/01). Coat color expected from breeding:Black
When using the 5LX- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004155 in your Materials and Methods section.