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This study assessed the metabolic and anatomical consequences of partial or complete depletion of this system in transgenic mice without cytosolic B\u2010CK (B\u2010CK\u2013\/\u2013), mitochondrial ubiquitous CK (UbCKmit\u2013\/\u2013), or both isoenzymes (CK \u2013\/\u2013), using non\u2010invasive quantitative magnetic resonance (MR) imaging and spectroscopy. MR imaging revealed an increase in ventricle size in a subset of B\u2010CK\u2013\/\u2013 mice, but not in animals with UbCKmit or compound CK mutations. Mice lacking single CK isoenzymes had normal levels of high\u2010energy metabolites and tissue pH. In the brains of CK double knockouts pH and ATP and Pi levels were also normal, even though PCr had become completely undetectable. Moreover, a 20\u201330% decrease was observed in the level of total creatine and a similar increase in the level of neuronal <jats:italic>N<\/jats:italic>\u2010acetyl\u2010aspartate compounds. Although CKs themselves are not evenly distributed throughout the CNS, these alterations were uniform and concordant across different brain regions. Changes in <jats:italic>myo<\/jats:italic>\u2010inositol and glutamate peaks did appear to be mutation type and brain area specific. Our results challenge current models for the biological significance of the PCr\u2013CK energy system and suggest a multifaceted role for creatine in the brain.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2004.02599.x","type":"journal-article","created":{"date-parts":[[2004,9,1]],"date-time":"2004-09-01T15:16:11Z","timestamp":1094051771000},"page":"1321-1330","source":"Crossref","is-referenced-by-count":52,"title":["Cerebral creatine kinase deficiency influences metabolite levels and morphology in the mouse brain: a quantitative <i>in vivo<\/i><sup>1<\/sup>H and <sup>31<\/sup>P magnetic resonance study"],"prefix":"10.1111","volume":"90","author":[{"given":"H. J. 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