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BioMed Research International
Volume 2013 (2013), Article ID 125492, 11 pages
http://dx.doi.org/10.1155/2013/125492
Research Article

A Novel Bone Morphogenetic Protein 2 Mutant Mouse, , Displays Impaired Intracellular Handling in Skeletal Muscle

1Department of Microbiology and Molecular Biology, Brigham Young University, 775-A WIDB, Provo, UT 84602, USA
2Department of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USA
3Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA

Received 18 June 2013; Revised 12 October 2013; Accepted 29 October 2013

Academic Editor: Kunikazu Tsuji

Copyright © 2013 Laura C. Bridgewater et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We recently reported a novel form of BMP2, designated nBMP2, which is translated from an alternative downstream start codon and is localized to the nucleus rather than secreted from the cell. To examine the function of nBMP2 in the nucleus, we engineered a gene-targeted mutant mouse model ( ) in which nBMP2 cannot be translocated to the nucleus. Immunohistochemistry demonstrated the presence of nBMP2 staining in the myonuclei of wild type but not mutant skeletal muscle. The mouse exhibits altered function of skeletal muscle as demonstrated by a significant increase in the time required for relaxation following a stimulated twitch contraction. Force frequency analysis showed elevated force production in mutant muscles compared to controls from 10 to 60 Hz stimulation frequency, consistent with the mutant muscle’s reduced ability to relax between rapidly stimulated contractions. Muscle relaxation after contraction is mediated by the active transport of Ca2+ from the cytoplasm to the sarcoplasmic reticulum by sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), and enzyme activity assays revealed that SERCA activity in skeletal muscle from mice was reduced to approximately 80% of wild type. These results suggest that nBMP2 plays a role in the establishment or maintenance of intracellular Ca2+ transport pathways in skeletal muscle.