Jump to content
Powered by

"Marathon mouse" runs with a gene defect

Researchers at the University Hospital of Heidelberg are investigating the effect of signalling substances on muscle development. If mice are missing a gene for a certain muscle protein, they become "marathon runners". In running tests, they have significantly more stamina than normal mice and the ability to run faster and further. Scientists at the University Hospital of Heidelberg have been able to show this effect in genetically modified mice whose muscles did not form the protein calsarcin 2. The work represents an important contribution towards understanding muscle development and is significant for research into and the possible treatment of cardiac weaknesses.

The reason for the improved endurance is that the lack of the protein calsarcin 2 leads to the muscles in “marathon mice” containing an unusually high concentration of slow muscle fibres. While the slow fibres do not react as quickly as rapid muscle fibre types, they can work longer. In contrast, rapid muscle fibre types react immediately, but are more quickly exhausted.

Normally, the proportion of different muscle fibre types is strongly regulated so that the muscles can optimally adapt to changing requirements. These adaptation processes depend on the interaction of calsarcin 2 with the muscle protein calcineurin, which promotes the generation of the long and persistent muscle fibres. “Normally, calsarcin 2 binds to calcineurin to control this protein’s activity,” explains Professor Dr. Norbert Frey. The researchers’ results show that the lack of calsarcin 2 leads to an increase in the effect of calcineurin, which results in the generation of more persistent muscle fibres.

Weak cardiac muscles = weak skeletal muscles?

But why are heart specialists so interested in skeletal muscles? “There are many similarities between the heart and skeletal muscles and many of the molecular mechanisms are the same. That is why we have decided to research the calsarcin protein family in greater detail so that we can gain a greater understanding of their function outside the heart,” said Professor Frey.

In addition, the performance capacity of patients with cardiac insufficiency depends largely on the condition of the skeletal muscles,” said Dr. Derk Frank, assistant doctor in Frey’s department and co-author of the paper. The cardiologists want to use their research to help understand if there is a connection between cardiac muscle fitness and skeletal muscle fitness on the molecular level.

The research done by the group of international researchers led by Professor Dr. Norbert Frey, formerly chief physician in the Department of Cardiology, Angiology and Pneumology (Medical Director: Professor Dr. Hugo A. Katus) at the Heidelberg University Hospital and since October 2008, Medical Director of the Hospital of Cardiology and Angiology in Kiel, has been published in the internationally renowned “Journal of Clinical Investigation”.

Literature:
Norbert Frey, Derk Frank, Stefanie Lippl, Christian Kuhn, Harald Kögler, Tomasa Barrientos, Claudia Rohr, Rainer Will, Oliver J. Müller, Hartmut Weiler, Rhonda Bassel-Duby, Hugo A. Katus and Eric N. Olson: Calsarcin-2 deficiency increases exercise capacity in mice through calcineurin/NFAT activation. J. Clin. Invest. doi:10.1172/JCI36277.


Source: University Hospital of Heidelberg press release - 4 November 2008
For further information please contact:
Dr. Derk Frank
Tel.: +49 (0)6221 / 56 398 30
E-mail: Derk.Frank@med.uni-heidelberg.de
Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/marathon-mouse-runs-with-a-gene-defect