Cerebellar defect and impaired motor coordination in mice lacking vimentin

Abstract

Vimentin belongs to the family of intermediate filament (IF) proteins. During the nervous system development in mammals, it is transiently expressed in precursor cells of neuronal and glial lineages, and then it is progressively replaced by other types of IF proteins. Surprisingly, mice knock-out for vimentin develop and reproduce without any apparent defects (Colucci-Guyon et al. Cell 79:679-694, 1994). In adult rodents, Bergmann glia (BG) of the cerebellum continue to express vimentin together with glial fibrillary acidic protein (GFAP). A careful analysis of cerebellar morphology and ultrastructure in mutants showed poorly developed and highly abnormal BG, whereas the migration of granular neurons proceeded normally. Moreover, many Purkinje cells (PC) appeared stunted with a loss of spiny branchlets, and some of them were necrotic. Finally, impaired motor coordination was evidenced by behavioral tests. These observations demonstrate a role for vimentin in contributing to the normal development and morphology of BG and reveal a hitherto unreported functional relationship between BG and PC.

Comparative anatomy of the cerebellar cortex in mice lacking vimentin, GFAP, and both vimentin and GFAP

“…However, granule cell migration during development of the three mutant mice was not impaired (Colucci-Guyon et al, 1999;A. Privat, unpublished results).…”

“…The structural abnormalities and signs of degeneration and necrosis found in PC and granule cells of VIM mutant mice were correlated with a deficit of motor coordination (Colucci-Guyon et al, 1999). Since BF constitute the insulating element of PC somata and processes in the molecular layer, the most likely hypothesis is that, in the absence of VIM, GEC are unable to support the homeostasis of PC function, which could explain why BF are hypertrophied.…”

“…Thus, the sole absence of VIM prevents GFAP assembly in an IF-network in GEC of the cerebellum, indicating that, in this cellular population, VIM is necessary for the organization and stabilization of GFAP filaments (Galou et al, 1996;Colucci-Guyon et al, 1999). On the contrary, in GFAP mutant mice, the sole absence of GFAP does not seem to affect VIM expression and organization into an IF network in GEC (Gomi et al, 1995;Shibuki et al, 1996).…”

“…These two single mutant mice produce two highly interesting situations. On the one hand (in VIM mutant mice), there is a total lack of glial filaments in GEC, whereas the remaining astroglial population is completely normal (Galou et al, 1996;Colucci-Guyon et al, 1999). By contrast (in GFAP mutant mice), there is a normal presence of VIM filaments in GEC, whereas the remaining astroglial population is totally devoid of glial filaments (Gomi et al, 1995;Shibuki et al, 1996).…”

“…GEC in mice lacking VIM exhibited processes totally devoid of glial filaments indicating the involvement of VIM in the GFAP assembly and stabilization (Galou et al, 1996). Moreover, mutant mice exhibit abnormal Purkinje cells (PC) and an impaired motor coordination (Colucci-Guyon et al, 1999).…”