TY - JOUR
T1 - Creatine kinase (CK) in skeletal muscle energy metabolism
T2 - A study of mouse mutants with graded reduction in muscle CK expression
AU - Van Deursen, Jan
AU - Ruitenbeek, Wim
AU - Heerschap, Arend
AU - Jap, Paul
AU - Ter Laak, Henk
AU - Wieringa, Bé
PY - 1994/9/13
Y1 - 1994/9/13
N2 - To understand better the role of the creatine kinase (CK)/phosphocreatine system in muscle bioenergetics, a series of mouse mutants with subnormal muscle CK (M-CK) expression has been generated. Here we compare the phenotypes of mice deficient in M-CK (M-CK(-/-)) and M-CK leaky-mutant mice, which carry a targeted insertion of a hygromycin B-poly(A) resistance cassette in the second M-CK intron. Mice homozygous for this M-CK allele (M- CK(I/I)) have a 3-fold reduction of dimeric muscle CK enzyme activity, whereas compound heterozygotes with the null M-CK allele (M-CK(I/-)) display a 6-fold reduction. Unlike M-CK(-/-) mice, these mutants have no increased glycogen content or glycogen consumption in their fast fibers. The intermyofibrillar mitochondrial volume of these fibers is also normal, suggesting that energy transport via the CK/phosphocreatine system may function at low myofibrillar M-band CK levels. Conversely, the flux of energy through the CK reaction is still not visible by means of 31P NMR spectroscopy, indicating that relatively high levels of M-CK expression (>34% of normal) are required to generate CK fluxes detectable by this technique. The ability of muscles to perform burst activity is also subnormal and closely correlates with the level of M-CK expression.
AB - To understand better the role of the creatine kinase (CK)/phosphocreatine system in muscle bioenergetics, a series of mouse mutants with subnormal muscle CK (M-CK) expression has been generated. Here we compare the phenotypes of mice deficient in M-CK (M-CK(-/-)) and M-CK leaky-mutant mice, which carry a targeted insertion of a hygromycin B-poly(A) resistance cassette in the second M-CK intron. Mice homozygous for this M-CK allele (M- CK(I/I)) have a 3-fold reduction of dimeric muscle CK enzyme activity, whereas compound heterozygotes with the null M-CK allele (M-CK(I/-)) display a 6-fold reduction. Unlike M-CK(-/-) mice, these mutants have no increased glycogen content or glycogen consumption in their fast fibers. The intermyofibrillar mitochondrial volume of these fibers is also normal, suggesting that energy transport via the CK/phosphocreatine system may function at low myofibrillar M-band CK levels. Conversely, the flux of energy through the CK reaction is still not visible by means of 31P NMR spectroscopy, indicating that relatively high levels of M-CK expression (>34% of normal) are required to generate CK fluxes detectable by this technique. The ability of muscles to perform burst activity is also subnormal and closely correlates with the level of M-CK expression.
KW - embryonic stem cells
KW - homologous recombination
KW - muscle bioenergetics
KW - phosphocreatine system
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U2 - 10.1073/pnas.91.19.9091
DO - 10.1073/pnas.91.19.9091
M3 - Article
C2 - 8090775
AN - SCOPUS:0028603394
SN - 0027-8424
VL - 91
SP - 9091
EP - 9095
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 19
ER -