Creatine kinase (CK) in skeletal muscle energy metabolism: A study of mouse mutants with graded reduction in muscle CK expression

Jan Van Deursen, Wim Ruitenbeek, Arend Heerschap, Paul Jap, Henk Ter Laak, Bé Wieringa

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9091-9095
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number19
DOIs
StatePublished - Sep 13 1994
Externally publishedYes

Fingerprint

MM Form Creatine Kinase
Creatine Kinase
Energy Metabolism
Skeletal Muscle
Muscles
Phosphocreatine
Glycogen
Hygromycin B
Alleles
Mitochondrial Size
Poly A
Heterozygote
Introns

Keywords

  • embryonic stem cells
  • homologous recombination
  • muscle bioenergetics
  • phosphocreatine system

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Creatine kinase (CK) in skeletal muscle energy metabolism : A study of mouse mutants with graded reduction in muscle CK expression. / Van Deursen, Jan; Ruitenbeek, Wim; Heerschap, Arend; Jap, Paul; Ter Laak, Henk; Wieringa, Bé.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 19, 13.09.1994, p. 9091-9095.

Research output: Contribution to journalArticle

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