Super-sniffer mice detect land mines, decode human olfactory system

In parallel, post-doctoral researcher Charlotte D’Hulst was trying to replace a mouse receptor gene with a human one. Even though such gene swapping is standard practice in other fields, it did not work. It wasn’t the first time researchers had been stymied by olfaction. Repeated attempts in the field to study odor receptors by growing them in cells in Petri dishes have also led to dead ends.

As a result, human olfaction receptors are poorly understood. “Without understanding how odors bind to receptors, people have no rational way of designing new odors,” says D’Hulst. “They also have no way of boosting the diminished smell capacity in patients with diseases such as Parkinson’s.”

So D’Hulst abandoned gene swapping and tried Feinstein’s transgenic super-sniffer technique to insert a human receptor gene into the mouse. It worked. “We have developed a system where we can study human odor receptors and finally determine how human odor coding works,” says Feinstein.

The team validated that the mice do indeed have an amplified sense of smell for the given receptor. They first used fluorescent imaging in live mice to trace the activation of the amplified odor receptor in response to the receptor’s corresponding odor. These tests gave visual confirmation that the receptors are functional and present in greater numbers than others.

In a standard behavioral test in which animals were trained to avoid an odor known to bind the transgenic receptor, the super-sniffer mice were able to detect the presence of this unpleasant odor in water at levels two orders of magnitude lower than those detectable by mice without super-sniffer abilities. “The animals could smell the odor better because of the increased presence of the receptor,” says D’Hulst.

The team is now working towards commercializing their technology and has founded a company called MouSensor, LLC. The Feinstein lab has received funding from the Department of Defense to develop super-sniffing rats that can be trained to detect TNT and potentially find land mines. The researchers also envision applications of the MouSensor for developing a type of nose-on-a-chip as a means of diagnosing disease using chemical detection profiling. “We have these millions-of-years-old receptors that are highly tuned to detect chemicals,” says Feinstein. “We think we can develop them into tools and use them to detect disease.”

— Read more in Charlotte D’Hulst et al., “MouSensor: A Versatile Genetic Platform to Create Super Sniffer Mice for Studying Human Odor coding,” Cell Reports (7 July 2016) (DOI: http://dx.doi.org/10.1016/j.celrep.2016.06.047); see also Michael Price, “These ‘supersniffer’ mice could one day detect land mines, diseases,” Science (7 July 2016)