Expression of functional mitochondrial creatine kinase in liver of
transgenic mice.
Miller, Kenneth, Kathy Sharer, Joe Suhan, Alan P. Koretsky.
Department of Biological Sciences and Pittsburgh NMR Center for
Biomedical Research, Carnegie Mellon University, Pittsburgh, PA
15213
APStracts 3:0373C, 1996.
The mitochondrial isoform of creatine kinase (Mi-CK) is localized to
the mitochondrial intermembrane space and its precise role in vivo is
still actively investigated. Here, we report a transgenic mouse model
in which Mi-CK is expressed in liver, a tissue that does not normally
express significant levels of CK. Expression of the genomic clone for
human, ubiquitous Mi-CK was controlled by the promoter/enhancer
region of the transthyretin gene. Three of seven founder mice were
chosen to establish lines and had Mi-CK activity ranging from 13 -
269 [mu]moles/min/gm wet weight. Differential centrifugation and
histochemical staining demonstrated that greater than 90% of the CK
activity is localized to the mitochondrial intermembrane space. An
unusual mitochondrial morphology characterized by an angular nature
to the membranes was detected using electron microscopy in the
transgenic line expressing the highest levels of Mi-CK. Increasing
hepatic total creatine levels led to a return to normal mitochondrial
morphology. 31P NMR spectroscopy demonstrated that the expressed Mi
-CK is capable of producing and utilizing phosphocreatine. These mice
will be useful for investigating gain of function effects of Mi-CK in
cellular energetics.
Received 17 January 1995; accepted in final form 7 November 1996.
APS Manuscript Number C27-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996