Structural and behavioural consequences of double deficiency for creatine kinases BCK and UbCKmit.
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. 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. This study shows that adult male mice lacking both creatine kinase isoforms (CK--/-- double knockout mice) have a reduced body weight, and demonstrate a severely impaired spatial learning in both a dry and a wet maze, lower nestbuilding activity and diminished acoustic startle reflex responses when compared to age-matched male wildtype mice with the same genetic background. In contrast, their visual and motor functions, exploration behaviour, prepulse inhibition and anxiety-related responses were not changed, suggesting no global deficit in sensorimotor function, hearing or motivation. Morphological analysis of CK--/-- double knockout brains revealed a reduction of approximately 7% in wet brain weight and hippocampal size, a approximately 15% smaller regio-inferior and relatively larger supra-pyramidal, and intra-infra-pyramidal mossy fiber areas. These results suggest that lack of both brain specific creatine kinase isoforms renders the synaptic circuitry in adult brain less efficient in coping with sensory or cognitive activity related challenges.
Streijger
Femke
F
Department of Cell Biology, NCMLS, UMC Radboud, University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Oerlemans
Frank
F
Ellenbroek
Bart A
BA
Jost
Carolina R
CR
Wieringa
Bé
B
Van der Zee
Catharina E E M
CE
D000161:Acoustic Stimulation; D000818:Animals; D001835:Body Weight / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000201:enzymology; D003402:Creatine Kinase / Q000172:deficiency / Q000378:metabolism*; D052276:Creatine Kinase, BB Form; D052281:Creatine Kinase, Mitochondrial Form; D004734:Energy Metabolism / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology*; D007527:Isoenzymes / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000201:enzymology; D009425:Nesting Behavior / Q000502:physiology; D013216:Reflex, Startle / Q000502:physiology*
D007527:Isoenzymes; D003402:Creatine Kinase; D052276:Creatine Kinase, BB Form; D052281:Creatine Kinase, Mitochondrial Form