Mice in Space

Guest Author: Catherine Hiller, Novartis

The Novartis Institutes for Biomedical Research (NIBR) will be sending a strain of mice to the International Space Station (ISSInternational Space Station) onboard the SpaceX-4 Dragon capsule, hopefully as early as Saturday, September 20. The mice will live in microgravityThe condition of perceived weightlessness created when an object is in free fall, for example when an object is in orbital motion. Microgravity alters many observable phenomena within the physical and life sciences, allowing scientists to study things in ways not possible on Earth. The International Space Station provides access to a persistent microgravity environment. during their mission, allowing scientists to learn more about muscle development and muscle atrophy.

The study marks two milestones: it’s the first time NIBR has collaborated with the Center for the Advancement of Science in Space (the ISS National Lab), the nonprofit organization that manages the ISS U.S. National Laboratory, and this investigation reinstitutes rodent research on the space station. The collaboration came about when the ISS National Lab encouraged David Glass, an executive director in the musculoskeletal disease research area at NIBR, to submit a proposal. Glass has co-authored about one hundred articles on the molecular mechanisms of muscle growth and muscle atrophy.

Muscle atrophy is of special significance to two populations: astronauts who spend time in space, and the elderly. Although astronauts exercise for at least two hours a day while they are in space, this does not compensate for the load loss they experience without gravity: some muscle atrophy sets in within days. Muscle atrophy is more gradual on earth, but every human experiences muscle loss as they get older. Muscle atrophy also plays a deleterious role in a number of serious diseases, including cancer.

Sam Cadena, NIBR program manager for the space mission and a lab head in NIBR’s Musculoskeletal group, explains that muscle atrophy affects more than just strength. “Muscles are the storage space for amino acids, the only reservoir for them,” he says. “If you lose muscle, you lose health.”

One way to lessen muscle atrophy is to down-regulate a protein called Muscle Ring Finger 1 (MuRF-1), which labels proteins for degradation, thereby hastening muscle loss. Glass discovered this protein and its role before arriving at Novartis. The mice traveling in space are MuRF-1 knockouts, which means they do not express MuRF-1. Consequently, they are resistant to losing muscle. These mice will be divided into two groups. One group will be sent to the ISS and the others will remain at NASA’s Kennedy Space Center. There will also be two groups of normal mice, one set on the ground and the other on station. “We expect that the muscles in the MuRF-1 knockout mice will atrophy much less than those in the control mice,” says Cadena.

His lab associate, Jason Gilbert, will help to evaluate changes in the muscles of the mice. The researchers will measure atrophy two ways—first by weighing the muscles and second by looking at cross sections of the muscles to determine the size of individual muscle fibers.

Kenneth Shields, director of operations at the ISS National Lab, is excited about the September launch. “We have a lot riding on this mission,” he says. Among other things, the ISS National Lab wants to “validate the hardware”—new housing for the mice. The Animal Enclosure Module is intended for long stays in orbit and has sophisticated feeding and filtering systems. This should ensure the mice are kept comfortable and healthy while on board the ISS.

Gilbert and Cadena hope the study will validate their mouse model and increase their understanding of the MuRF-1 protein. It might even accelerate the pace of drug discovery in the field. To complement the study, there will be a second mice in space mission in February.