Disease relevance of Ckb

• Electron microscopic analyses have established that fibrosis is not a factor that determines BCK mRNA levels in the chronically denervated or denervated-reinnervated muscles [1].

Psychiatry related information on Ckb

• This task performance deficit persisted in 24-month-old, aged B-CK-/- mice, on top of the age-related memory decline normally seen in old animals [2].

High impact information on Ckb

• The M isoform of creatine kinase (MCK), the striated muscle-specific isoform, is expressed later than BCK [3].
• In the mouse, myogenin, first detected at 8.5 days p.c., is expressed at the same time as BCK in myotomes [3].
• In the mouse, BCK transcript levels fall of rapidly in striated muscle shortly after the onset of MCK gene expression [3].
• Using isoform-specific 35S-labeled antisense cRNA probes for in situ hybridization, we have detected BCK mRNAs in embryonic mouse and chick myotomes, the first skeletal muscle masses to form in developing embryos [3].
• The B isoform of creatine kinase (BCK), which is expressed at a high level in embryonic neural tissues, is also expressed abundantly in developing striated muscle and is an early marker for skeletal myogenesis [3].

Biological context of Ckb

• Using targeting constructs based on strain 129/Sv isogenic DNA we managed to ablate the essential exons of the B-CK and M-CK genes at reasonably high frequencies [4].
• Previously, we reported that mice deficient for BCK or UbCKmit each showed a surprisingly mild phenotype, probably due to reciprocal functional compensation by the remaining creatine kinase [5].
• To characterize the transcriptional regulatory mechanisms, a chimeric construct containing 1.2 kilobase pairs of 5'-flanking DNA from the human BCK gene placed upstream of the chloramphenicol acetyltransferase gene in the promoterless plasmid pSVOCAT was transiently transfected into C2C12 cells [6].

Anatomical context of Ckb

• BCK is expressed at high levels in both skeletal and cardiac muscle in mouse and chick embryos [3].
• Data suggest that: 1) the level of BCK mRNA accumulation in innervated hindlimb muscles peaks at E16.5 and remains at fetal levels until the second month postnatal, when it falls to the level found in the adult [7].
• The cytosolic brain-type creatine kinase (BCK) isoform and the mitochondrial ubiquitous creatine kinase (UbCKmit) isoform are both important for the maintenance and distribution of cellular energy in neurons and astrocytes [5].
• Finally, we demonstrate that UbCKmit has a widespread occurrence in the cell soma of neuronal nuclei along the rostro-caudal axis of the brain, i.e. cortex, midbrain, hindbrain, cerebellum and brainstem, similar to the occurrence of B-CK [8].
• Brain-type creatine kinases B-CK (cytosolic) and UbCKmit (mitochondrial) are considered important for the maintenance and distribution of cellular energy in the central nervous system [8].

Associations of Ckb with chemical compounds

• It is suggested that the persistent expression of the mitochondrial isoform ubiquitous mitochondrial CK (UbCKmit) in the creatine/phospho-creatine shuttle provides compensation for the loss of B-CK in the brain [2].
• Finally, a delayed development of pentylenetetrazole-induced seizures (creating a high-energy demand) was observed in B-CK-/- mice [2].
• We predict that the remaining functional intactness of the cytosolic B-CK reaction and perhaps the compensatory role of other phosphoryl transfer systems are sufficient to sustain the energy requirements for basic sensory, motor and physiological activities in UbCKmit-/- mice [8].
• Accordingly, BCK promoter constructs were transiently transfected into C2C12 cells and, after a switch to differentiation medium, were treated with bFGF, bFGF plus herbimycin, adenosine 3',5'-cyclic monophosphate (cAMP), or phorbol 12-myristate 13-acetate (PMA) [9].

Other interactions of Ckb

• This study assessed the metabolic and anatomical consequences of partial or complete depletion of this system in transgenic mice without cytosolic B-CK (B-CK-/-), mitochondrial ubiquitous CK (UbCKmit-/-), or both isoenzymes (CK -/-), using non-invasive quantitative magnetic resonance (MR) imaging and spectroscopy [10].
• Previously, we have demonstrated an abnormal behavioral phenotype in mice lacking the B-CK creatine kinase isoform, regarding exploration, habituation, seizure susceptibility and spatial learning [8].

Analytical, diagnostic and therapeutic context of Ckb

• We characterized the developmental expression of the brain creatine kinase (BCK) gene in the C2C12 myogenic cell line with the use of isoenzyme, Western blot, and Northern blot analyses [6].

References