Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene.
Intracellular calcium-binding proteins are abundantly expressed in many neuronal populations. Previous evidence suggests that calcium-binding proteins can modulate various neuronal properties, presumably by their action as calcium buffers. The importance of calcium-binding proteins for nervous system function in an intact integrated system is, however, less clear. To investigate the physiological role of a major endogenous calcium-binding protein, calbindin D28k (calbindin) in vivo, we have generated calbindin null mutant mice by gene targeting. Surprisingly, calbindin deficiency does not affect general parameters of development and behavior or the structure of the nervous system at the light microscopic level. Null mutants are, however, severely impaired in tests of motor coordination, suggesting functional deficits in cerebellar pathways. Purkinje neurons, the only efferent of the cerebellar cortex, and inferior olive neurons, the source of the climbing fiber afferent, have previously been shown to express calbindin. Correlated with this unusual type of ataxia, confocal calcium imaging of Purkinje cells in cerebellar slices revealed marked changes of synaptically evoked postsynaptic calcium transients. Their fast, but not their slow, decay component had larger amplitudes in null mutant than in wild-type mice. We conclude that endogenous calbindin is of crucial importance for integrated nervous system function.
Airaksinen
M S
MS
Department of Neurochemistry, Max Planck Institute for Psychiatry, Martinsried, Germany.
Eilers
J
J
Garaschuk
O
O
Thoenen
H
H
Konnerth
A
A
Meyer
M
M
D000818:Animals; D001259:Ataxia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D001522:Behavior, Animal; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005071:Evoked Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D011597:Psychomotor Performance; D011689:Purkinje Cells / Q000502:physiology; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology; D015854:Up-Regulation
C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G; D002118:Calcium