These Lta4h knock-out mice exhibit resistance to platelet-activating factor induced systemic shock.
Beverly H Koller, University of North Carolina at Chapel Hill
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.
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 blastocysts. The resulting chimeric animals were backcrossed to 129 mice (mixed 129P2;129S6).
|Allele Name||targeted mutation 1, Beverly H Koller|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||LtA4 hydrolase-|
|Gene Symbol and Name||Lta4h, leukotriene A4 hydrolase|
|Strain of Origin||129P2/OlaHsd|
|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.|
|Mutations Made By|| |
Beverly Koller, University of North Carolina at Chapel Hill
This strain originated on a 129P2 background and was backcrossed once on the 129S6 background before being made homozygous. When maintaining a live colony, these mice can be bred as homozygotes.
When using the LtA4 hydrolase- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004446 in your Materials and Methods section.