By Catherine Hiller

No, “Mice in Space” is not the latest Disney movie! It’s a study in which a specific strain of mice, developed at the Novartis Institutes for BioMedical Research (NIBR), will be sent to the International Space Station (ISS) on September 20. The mice will live in microgravity during their mission, allowing scientists to learn more about muscle development and muscle atrophy.

The study marks two firsts: it’s the first time NIBR has collaborated with the Center for the Advancement of Science in Space (CASIS), the nonprofit organization that manages the ISS National Laboratory, and it’s the first time any non-human mammals will live aboard the space station. The collaboration came about when CASIS 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: people who spend time in space, and people who are, or plan to be, old. 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 being 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.”

Cadena has been working in the lab with the mice that will go to the space station. He began studying muscle because of his lifelong interest in exercise and nutrition.

“I’m from a Hispanic background where there’s a lot of fried food,” he says. “But my parents were influenced by the Pritikin diet. So we went from fried tortillas made with lard to tortillas baked in the oven with bran flakes—which tasted terrible.”

Cadena’s first foray into space-related research was as a graduate student. At the Tufts School of Nutrition, he performed a bed rest study funded by NASA. Some study participants, while supine, did rigorous exercise with bungee-type rubber bands. These fared much better than the supine controls who hadn’t exercised. When Cadena heard that David Glass was forming a group at NIBR to work on the molecular signals involved in muscle loss, he jumped at the chance to join in. “I never thought I would work with someone I’d followed so closely.”

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 hardy mice will be divided into two groups: “mousetronauts” that will be sent into space and others that will remain at the Kennedy Space Center. There will also be two groups of normal mice, on ground and on high. “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.

“I wish I could go up there with the mice in space,” Gilbert says. “I joke that if something goes wrong, I’ll go up and fix it.”

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.

Kenneth Shields, director of operations at CASIS, is excited about the September launch. “We have a lot riding on this mission,” he says. Among other things, CASIS 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.

According to the latest YELP (and SQUEAK) reviews, this deluxe mouse hotel is out of this world!

Photo: Novartis researchers Sam Cadena (right) and Jason Gilbert are preparing mice for a trip to the International Space Station.

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