Motor discoordination of transgenic mice overexpressing a microtubule destabilizer, stathmin, specifically in Purkinje cells.
The proper regulation of microtubule (MT) structure is important for dendritic and neural circuit development. However, the relationship between the regulation of the MTs in dendrites and the formation of neural function is still unclear. Stathmin is a MT destabilizer, and we have previously reported that the expression and the activity of stathmin is downregulated during cerebellar Purkinje cell (PC) development. In this study, we generated transgenic mice that specifically overexpress the constitutively active form of stathmin in the PCs. These mutant mice did not show any obvious morphological or excitatory transmission abnormalities in the cerebellum. In contrast, we observed a decline in the expression of MAP2 and KIF5 signal in the PC dendrites and a discoordination of motor function in the mutant mice, although they displayed normal general behavior. These data indicate that the overexpression of stathmin disrupts dendritic MT organization, motor protein distribution, and neural function in PCs.
Ohkawa
Noriaki
N
Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan.
Hashimoto
Kouichi
K
Hino
Toshiaki
T
Migishima
Rika
R
Yokoyama
Minesuke
M
Kano
Masanobu
M
Inokuchi
Kaoru
K
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D002531:Cerebellum / Q000166:cytology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D016547:Kinesins / Q000378:metabolism; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics; D019957:Motor Skills Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism* / Q000502:physiology; D014404:Tubulin / Q000378:metabolism
D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009414:Nerve Growth Factors; C491794:Stmn4 protein, mouse; D014404:Tubulin; D016547:Kinesins