AOAH-/- KO mice have a neo cassette replacing exon 1, containing the translation start codon, of the acyloxyacyl hydrolase (Aoah) gene, abolishing gene function. AOAH is an enzyme found in dendritic cells (DCs), neutrophils, NK cells, monocytes, macrophages and renal proximal tubule cells that can remove secondary fatty acyl chains from the lipid A regions of diverse lipopolysaccharides (LPS). Deacylation of LPS is a mechanism by which vertrbrates may modulate host responses to the bacterial agonist. Mice homozygous for this allele are viable and fertile, and mice are normal until challenged parenterally with LPS. Subsequent to LPS exposure, they develop high polyclonal antibody titers, massive hepatomegaly, and prolonged endotoxin tolerance. After a single low dose intraperitoneal exposure to hexaacyl LPS, induced tolerance lasts for several weeks longer than that seen in wildtype animals. These mice are unable to regain normal immune responsiveness for many weeks/months after they are exposed in vivo to a small amount of LPS or Gram-negative bacteria. Although AOAH also has activity in vitro as a (phospho)lipase A1, in vivo substrates other than LPS have not been identified so far.
