Mice that lack a particular gene die suddenly and without overt signs of illness in response to an infection that is usually harmless, according to a study to be published online in Nature Genetics. This work may lead to new insights into the origins of sudden death in humans, although such a link has not yet been made.
Bruce Beutler and colleagues treated mice with a chemical mutagen -- an agent that changes genetic information; and examined the third-generation offspring of the mutant mice for susceptibility to cytomegalovirus (CMV). This virus, at the dose delivered, is normally harmless. The progeny of four of the original mutants, however, died suddenly between 36 hours and 3 days after inoculation. One of these lines has a large deletion in Kcnj8, a gene encoding a component of a potassium channel expressed in smooth muscle and endothelial cells of the coronary artery (two of the other lines carry different mutations in Kcnj8).
The protein that interacts with Kcnj8 has a counterpart in the fruit fly, and the authors show that it similarly protects flies against sudden death after challenge with flock house virus (FHV). The authors propose that this potassium channel is required for the coronary arteries to survive the systemic metabolic stress and arterial constriction that accompanies the innate immune response to viruses such as CMV and FHV.
Bruce Beutler (Scripps Research Institute, La Jolla, CA, USA)
Abstract available online.
(C) Nature Genetics press release.
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