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1 Orthopedics and Biomedical Sciences, UCSD, La Jolla, California, United States
2 Medicine, Univ. California San Diego, La Jolla, California, United States
3 Orthopaedics and Bioengineering, University of California, San Diego, California, United States
4 Muscle Biology Laboratory, University of Wisconsin, Madison, Wisconsin, United States
* To whom correspondence should be addressed. E-mail: rlieber{at}ucsd.edu.
The biological response of muscle to eccentric contractions (ECs) results in strengthening and protection from further injury. However, the cellular basis for this response remains unclear. Previous studies identified the Muscle Ankyrin Repeat Protein family, consisting of Cardiac Ankyrin Repeat Protein (CARP), Ankyrin-repeat domain 2/Ankyrin Repeat Protein with PEST and Proline-Rich Region (Ankrd2/Arpp), and Diabetes Associated Ankyrin Repeat Protein (DARP), as rapidly and specifically upregulated in mice after a single bout of EC. To determine the role of these genes in skeletal muscle, a survey of skeletal muscle structural and functional characteristics was performed on mice missing all three MARP family members (MKO). There was a slight trend towards MKO muscles having a slower fiber type distribution but no differences in muscle fiber size. Single MKO fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wildtype counterparts, indicating that these proteins may play a role in the passive mechanical behavior of muscle. Finally, MKO mice showed a greater degree of torque loss after a bout of ECs compared to wildtype mice, although they recovered from the injury with the same or even improved time course. This recovery was associated with enhanced expression of the muscle regulatory genes MyoD and muscle LIM protein, suggesting that the MARP family may play both important structural and gene regulatory roles in skeletal muscle.
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