Motor discoordination of transgenic mice overexpressing a microtubule destabilizer, stathmin, specifically in Purkinje cells

Neurosci Res. 2007 Sep;59(1):93-100. doi: 10.1016/j.neures.2007.06.1464. Epub 2007 Jun 14.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Behavior, Animal
  • Cerebellum / cytology
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Excitatory Postsynaptic Potentials / radiation effects
  • Exploratory Behavior / physiology
  • Gene Expression Regulation / genetics*
  • In Situ Hybridization
  • In Vitro Techniques
  • Kinesins / metabolism
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Motor Activity / genetics
  • Motor Skills Disorders / genetics*
  • Motor Skills Disorders / pathology
  • Motor Skills Disorders / physiopathology
  • Nerve Growth Factors / genetics*
  • Nerve Growth Factors / metabolism*
  • Purkinje Cells / metabolism*
  • Purkinje Cells / physiology
  • Tubulin / metabolism

Substances

  • Microtubule-Associated Proteins
  • Mtap2 protein, mouse
  • Nerve Growth Factors
  • Stmn4 protein, mouse
  • Tubulin
  • Kinesins