For humans, this work could lead to a genetic switch, or drug, that allows people to grow new muscle cells to replace those that are damaged, worn out, or not working for other reasons (e.g., muscular dystrophy). In addition, this same discovery also gives researchers a new tool for the study of difficult-to-treat muscle cancers. The full report containing details of this advance is available online in The FASEB Journal (fasebj).

"We hope that the genetically-engineered mouse models we developed will help scientists and clinicians better understand how to make muscle stem cells regenerate muscle tissue," said Charles Keller, M.D., assistant professor at the University of Texas Health Science Center and a senior researcher involved in the work. "For our own work on childhood muscle cancers, we also hope to understand how tumors start and progress, and to develop therapies that are less toxic than chemotherapy."

The scientists made their discovery by breeding special mice with a specific gene, called "Cre," which, when activated, can trigger mutations in muscle stem cells. This Cre trigger is restricted to muscle stem cells and requires a special drug for it to be activated. In one part of the study, using fluorescent techniques, the researchers were able to visualize stem cells and their derivatives in order to pinpoint exactly where muscle tissue was being made. In another part of the study, the scientists were able to activate tumor-causing mutations in muscle stem cells, providing valuable insights into the origins of muscle tumors, which have been previously elusive.

"This is basic science at its best," said Gerald Weissmann, M.D, Editor-in-Chief of The FASEB Journal . "This study in mice has not only shown us how stem cells turn into muscle in the living body, but brought us closer to the day when we can use stem cells to repair wounded flesh or a maimed physique."

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"This proves that changes in levels of these two MHC molecules is enough to account for both changes in motor learning and the ease of strengthening or weakening connections in the cerebellum," Shatz said. "It implies that, normally, these molecules are putting a brake on the nervous system's ability to alter its circuitry in response to changing experiences. When you take the MHC molecules away, you remove the brake."

In the wild state, motor performance - running from predators, chasing down meat - is a nice thing to have. If the K- and D-deficient mice learn and retain motor skills better, why doesn't evolution select for the deficient mice? Said Schatz: "Several other forms of learning besides motor learning - cognitive learning, spatial learning, recognition - don't take place in the cerebellum. There may be tradeoffs between one kind of learning and another - you're better able to escape but don't know exactly what to do in the next environment you encounter after running away - as well as between learning ability and circuit stability. More-easily altered circuitry might also be more prone to epilepsy."

The Stanford researchers have found other MHC molecules expressed in other types of neurons in other parts of the brain. "These molecules keep showing themselves to be important in limiting how much circuits can change by strengthening or weakening connections between nerve cells. We think they're going to figure as important players in many neurological disorders," Shatz said, noting a tantalizing if still controversial link between immune function and developmental brain disorders such as autism and schizophrenia.

"Traditionally, there's been a kind of provincialism about molecules," she said. "You know, 'Some molecules are used only by the immune system, other ones only by neurons.' But I think the assumption that the immune system would have sole ownership over these molecules is pretty naive.

"We could have ignored this finding. We could have said, 'Well, MHC isn't supposed to be there, so it must be an artifact.' And we would have missed one of the most exciting aspects of doing research, which is the unexpected."

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