title: Use of gene targeting for compromising energy homeostasis in neuro-muscular tissues: the role of sarcomeric mitochondrial creatine kinase.
abstract: We have introduced a single knock-out mutation in the mitochondrial creatine kinase gene (ScCKmit) in the mouse germ line via targeted mutagenesis in mouse embryonic stem (ES) cells. Surprisingly, ScCKmit -/- muscles, unlike muscles of mice with a deficiency of cytosolic M-type creatine kinase (M-CK -/-; Van Deursen et al. (1993) Cell 74, 621-631), display no altered morphology, performance or oxidative phosphorylation capacity. Also, the levels of high energy phosphate metabolites were essentially unaltered in ScCKmit mutants. Our results challenge some of the present concepts about the strict coupling between CKmit function and aerobic respiration.
authors.affiliation: Department of Cell Biology and Histology, Faculty of Medical Sciences, University of Nijmegen, Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Steeghs
authors.forename: A
authors.initials: A
authors.lastname: Heerschap
authors.forename: A
authors.initials: A
authors.lastname: de Haan
authors.forename: W
authors.initials: W
authors.lastname: Ruitenbeek
authors.forename: F
authors.initials: F
authors.lastname: Oerlemans
authors.forename: J
authors.initials: J
authors.lastname: van Deursen
authors.forename: B
authors.initials: B
authors.lastname: Perryman
authors.forename: D
authors.initials: D
authors.lastname: Pette
authors.forename: M
authors.initials: M
authors.lastname: Brückwilder
authors.forename: J
authors.initials: J
authors.lastname: Koudijs
authors.forename: P
authors.initials: P
authors.lastname: Jap
authors.forename: B
authors.initials: B
authors.lastname: Wieringa
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000235:genetics / Q000502:physiology*; D004734:Energy Metabolism / Q000235:genetics*; D018390:Gene Targeting; D006706:Homeostasis / Q000235:genetics*; D007527:Isoenzymes; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008931:Mitochondria, Muscle / Q000201:enzymology*; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000201:enzymology; D010085:Oxidative Phosphorylation; D010725:Phosphocreatine / Q000096:biosynthesis; D012518:Sarcomeres / Q000201:enzymology*
chemical_list: D007527:Isoenzymes; D009124:Muscle Proteins; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase