Cerebellar protein expression in three different mouse strains and their relevance for motor performance.
The present study uses a proteomic approach to link motor function to cerebellar protein expression in 129X1/SvJ, C57BL/6J and nNOS WT mice. Poor performance on the Rota rod, the standard test for motor coordination, was detected in 129X1/SvJ mice. No gross impairments of neurological, cognitive and behavioural functions were observed. Identification and quantification of 48 proteins revealed reduced expression of calbindin, septin 5 and syntaxin binding protein 1 in 129X1/SvJ. In nNos WT glucose-6-phosphate 1 dehydrogenase X was decreased whereas dihydropyrimidinase-related protein-4 was increased. In C57BL/6J stress-70 protein, alpha enolase, NAD-dependent deacetylase sirtuin 2, septin 2, dihydropyrimidinase-related protein-2 and brain derived neurotrophic factor showed elevated levels. Neurological examination, Rota rod test, Morris Water Maze, Multiple-T-Maze, Open field and Elevated plus-maze were employed to study motor, cognitive and behavioural function. Mice were sacrificed and cerebellar tissue was homogenized. Proteins were extracted and separated on two-dimensional gel electrophoresis with subsequent in-gel digestion followed by mass spectrometrical analysis of peptides (MALDI-TOF/TOF-TOF). Quantification of spots was carried out by specific software. A strong association of impaired motor function with altered cerebellar protein expression of calbindin, septin 5 and syntaxin binding protein 1in 129X1/SvJ was observed and is in agreement with previous observations of motor deficiencies in a calbindin knock-out mouse. These results have to be taken into account when using 129X1/SvJ for biochemical, toxicological or gene targeting experiments as well as when studying the above-mentioned proteins or corresponding pathways and cascades in this mouse strain.
Pollak
Daniela
D
Department of Pediatrics, Division of Basic Science, Medical University of Vienna, Währinger Gürtel 18, A-1090 Vienna, Austria.
Weitzdoerfer
Rachel
R
Yang
Yae-Won
YW
Prast
Helmut
H
Hoeger
Harald
H
Lubec
Gert
G
D000818:Animals; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology; D001341:Autonomic Nervous System / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D004856:Postural Balance; D011597:Psychomotor Performance / Q000502:physiology*; D012677:Sensation / Q000502:physiology; D013045:Species Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D009419:Nerve Tissue Proteins; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse