Developmental expression of sarcomeric and ubiquitous mitochondrial creatine kinase is tissue-specific

Creatine kinase (CK) isoenzymes play prominent roles in myocardial energy metabolism. Two nuclear genes encode mitochondrial creatine kinase (MtCK), are tissue-specific in their expression, and are thus designated as sarcomeric MtCK (sMtCK) and ubiquitous MtCK (uMtCK). Quantitative analysis of the mRNA expression of both MtCKs in developing rat tissues demonstrates tissue-specific developmental regulation. sMtCK mRNA in heart is undetectable prenatally but is dramatically upregulated by 28 d postnatally. sMtCK mRNA in skeletal muscle is also extremely low prenatally but is markedly upregulated at birth and doubles by 28 d postnatally. uMtCK mRNA expression is present at low levels in fetal brain and intestine. Brain uMtCK mRNA continues to rise from -4 d prenatally until 28 d postnatally (6-fold increase), but intestinal uMtCK mRNA increases immediately prior to birth, falls, and is upregulated again at 28 d (20-fold). uMtCK mRNA is undetectable in fetal skeletal muscle or heart, but increases to low levels in skeletal muscle at birth and remains at this level into adulthood. uMtCK is not detectable in heart, lung, testes, or liver at any stage examined. We conclude that sMtCK and uMtCK are developmentally regulated in a tissue-specific manner. Unlike cytosolic muscle CK and brain CK, there is no isoenzyme switch between sMtCK and uMtCK in the developing animal. Our results suggest that specific trans-acting factors regulate the different developmental and tissue-specific expression of the MtCK genes.