Mice bearing a targeted inactivation of nBmp2 show decreased muscle strength

Abstract

An important growth factor in the body, bone morphogenetic protein (Bmp2) contributes to mesoderm formation, heart development, neurogenesis, skeletal development, and axis formation. We have recently discovered a novel variant of this protein in the nucleus (nBmp2). This protein is produced by translation from a downstream alternative start codon and is localized to the nucleus by means of a bipartite nuclear localization signal. To determine the function of nBmp2, a mouse was engineered in which the conventional Bmp2 growth factor is still expressed normally, but the nuclear variant, nBmp2, cannot be translocated to the nucleus. The mice appear phenotypically normal at birth and are fertile. A series of flexed limb‐hang strength tests, however, revealed that mutant mice have significantly reduced strength compared to wild type mice. Western blot analysis performed on mitochondrial extracts showed increased amounts of cytochrome C in mutant compared to wild type muscle mitochondria. These results suggest that nBmp2 may affect muscle strength by playing a role in mitochondrial function. This work was supported by NIH grant AR48839 and by an award from the Fulton Family Foundation to promote undergraduate research.