[Abstract Title]. - Society for Neuroscience

often exhibits diverse psychiatric symptoms. In the previous studies, we reported that Sgce
knockout mice lacking exon 4 exhibit myoclonus, motor deficits and alterations in emotional
responses and striatal monoamine metabolism. We also reported that striatum-specific
conditional knockout mice exhibited motor deficits in rotarod and beam-walking tests. To
analyze the contribution of other brain regions to the pathogenesis of this disease, we produced
Purkinje cell-specific Sgce conditional knockout and cerebral cortex-specific conditional
knockout mice and performed rotarod and beam-walking tests. Although cerebral cortex-specific
KO mice did not exhibit any motor defects in these tests, Purkinje cell-specific KO mice exhibit
significant motor learning defects in beam-walking test. The result suggested that ε-sarcoglycan
have an essential function in Purkinje cells for the motor learning.
Disclosures: F. Yokoi , None; M.T. Dang, None; Y. Li, None.
Poster
248. Dystonia
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 248.14/U13
Topic: C.03.j. Dystonia
Title: Physiological conditions induce dissociation of the 900 kDa neurotoxin type A complex
from Clostridium Botulinum
Authors: K. H. EISELE, H. V. TAYLOR, *K. B. FINK;
Biotech., Merz Pharmaceuticals, Frankfurt, Germany
Abstract: The objective of this study was to assess the stability of the 900 kDa botulinum
neurotoxin type A complex from clostridium botulinum and its dissociation kinetics under
physiological conditions.
Botulinum neurotoxin type A finally cleaves SNAP25 thus inhibiting exocytotic neurotransmitter
release. It is clinically used for treatment of various neurological disorders such as cervical
dystonia. The medicinal botulinum neurotoxin type A product Xeomin(1) consists of the 150
kDa neurotoxin molecule free of complexing proteins. In contrast, first-generation botulinum
neurotoxin type A products contain the 900 kDa neurotoxin complex consisting of the 150 kDa
neurotoxin molecule and several non-toxic proteins known as complexing proteins as produced
by the Clostridium Botulinum bacterium. It has been suggested that these complexing proteins
serve to prolong neurotoxin persistence and inhibit neurotoxin diffusion into adjacent tissues.
The 900 kDa botulinum neurotoxin type A complex was exposed to pH values from 6.0 to 7.6
and then separated by anion exchange HPLC to differentiate between the resulting neurotoxin
entities. Separation conditions were qualified by Western blotting using antibodies directed