Changes in mRNA expression profile underlie phenotypic adaptations in creatine kinase-deficient muscles

We have studied the mechanisms that regulate the remodeling of the glycolyt ic, mitochondrial and structural network of muscles of creatine kinase M (M -CK)/sarcomeric mitochondrial creatine kinase (ScCKmit) knockout mice by co mparison of wild-type and mutant mRNA profiles on cDNA arrays. The magnitud es of changes in mRNA levels were most prominent in M-CK/ScCKmit (CK-/-) do uble mutants but did never exceed those of previously observed changes in p rotein level for any protein examined. In gastrocnemius of CK-/- mice we me asured a 2.5-fold increase in mRNA level for mitochondrial encoded cytochro me c oxidase (COX)-III which corresponds to the increase in protein content . The level of the nuclear encoded mRNAs for COX-IV, H+-ATP synthase-C, ade nine nucleotide translocator-1 and insulin-regulatable glucose transporter- 4 showed a 1.5-fold increase, also in agreement with protein data. In contr ast, no concomitant up-regulation in mRNA and protein content was detected for the mitochondrial inorganic phosphate-carrier, voltage-dependent anion channel and certain glycolytic enzymes. Our results reveal that regulation of transcript level plays an important role, but it is not the only princip le involved in the remodeling of mitochondrial and cytosolic design of CK-/ - muscles. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.