USE OF GENE TARGETING FOR COMPROMISING ENERGY HOMEOSTASIS IN NEUROMUSCULAR TISSUES - THE ROLE OF SARCOMERIC MITOCHONDRIAL CREATINE-KINASE

We have introduced a single knock-out mutation in the mitochondrial cr eatine kinase gene (ScCKmit) in the mouse germ line via targeted mutag enesis in mouse embryonic stem (ES) cells. Surprisingly, ScCKmit -/- m uscles, unlike muscles of mice with a deficiency of cytosolic M-type c reatine kinase (M-CK -/-; Van Deursen et al, (1993) Cell 74, 621-631), display no altered morphology, performance or oxidative phosphorylati on capacity. Also, the levels of high energy phosphate metabolites wer e essentially unaltered in ScCKmit mutants, Our results challenge some of the present concepts about the strict coupling between CKmit funct ion and aerobic respiration.