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No Use Moving the Cheese

Christopher Brodie

Superman has super-hearing. Spider-Man has an uncanny "spider sense." But truth can be stranger than fiction. The newest superhero doesn't wear a cape or mask. It's a mouse, and it looks just like its normal brethren. Its super power is its amazing … nose. In a paper published in the February 5 issue of Neuron, collaborators at Florida State University and Yale University describe what they call "super-smeller" mice. These exceptional creatures have noses that are 1,000 to 10,000 times more sensitive than those of ordinary mice.

The superhero origin of these rodents involves the deletion, or knockout, of a gene. This technique usually generates mice that are quite sick, as nearly all mutations are harmful. Yet it doesn't seem to be true for this gene, Kv1.3, which encodes a protein that acts as a channel to let potassium ions (K+) into cells. This particular ion channel is found in immunological T-cells and neurons in the hippocampus and the olfactory bulb—the part of the brain that gets information from odor receptors in the nose.

In neurons, K+ channels such as Kv1.3 can act like governors on an engine, restricting the firing rate of the electrical spikes known as action potentials. The deletion of Kv1.3 removes this block. Using mice generated in the Yale lab of Richard Flavell, a team at Florida State led by Debra Fadool discovered that the loss of the channel caused one type of olfactory neuron, the mitral cell, to fire at lower thresholds and higher frequencies. Furthermore, the mutant cells were insensitive to chemical messages that normally rein in the flow of electrical current during an action potential. According to coauthor Leonard Kaczmarek, whose group at Yale studies the ion-channel biology of sensation, these changes resulted in greater excitability and better timing—effectively "phase locking" the output of the mitral cells, and thereby increasing the coherence of olfactory signals.

The mutation also caused structural changes in the olfactory bulb. In this part of the brain, olfactory receptor cells connect to mitral cells in clusters called glomeruli. The knockout mice had glomeruli that were about half as large—but twice as abundant—as normal. As a result, information from the nose went to twice as many "processing units" as usual. Fadool suggests this might increase the resolution of the signal—meaning that a faint odor would be more likely to be noticed above the jumble of background smells. 

Mutant mice could distinguish between complex odors, such as peppermint and powdered food, with nearly 15 times the sensitivity of normal mice. They were also better at detecting subtle molecular differences between odorants, such as some (but not all) closely related alcohols. The most amazing change was a huge increase in sensitivity: Mutants were able to perceive an odor that was 1,000 times more dilute than what wild type mice could smell.

The super-smeller was definitely a surprise—none of the investigators intended to create such a creature. "We had no inkling," states Kaczmarek. "We were looking for an effect in the auditory system." A chance meeting between Fadool and Kaczmarek in the mailroom of the Marine Biological Laboratory at Woods Hole, Massachusetts, prompted the collaboration.

As for commercial applications of the mice—bomb-sniffing mice, perhaps?—Kaczmarek says that while such droll uses have been mentioned, the investigators haven't been approached by eager entrepreneurs or government agents. "I don't think it would work," he quipped. "You'd have to have the mouse on a leash so it wouldn't get loose in the airplane." I guess The Adventures of Super-Smeller and the Sky Marshals will have to wait.

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