Abstracts (poster) - Wissenschaft Online

Stephan Hupfer, Julia Brill, Cord-Michael Becker, Kristina Becker
The entla mouse - a model for human absence epilepsy
Starting from motor abnormalities and a phenotype remniscent of petit mal epilepsy, we
were able to identify the gene defect of the recessive mouse mutant entla by genomewide
linkange analysis (1). This mouse suffers from absence epilepsy, with additional
ataxia as well as paroxysmal dyskinesia evident by postnatal week 4. The entla genome
harbours a mutation within the Cacna2d2 gene, coding for the accessory calcium
channel subunit α2δ2. Comparable Calcium channel defects can be found in the mutants
ducky, stargazer and tottering. These mutants however are often fatal and thus not well
suited for more thorough pathophysiological studies on the course of the disease. Closer
examination of the entla α2δ2 defect in recombinant systems showed changes in
processing as well as in targeting to the plasma membrane. Electrophysiologically, a
reduced Barium current density (pA/pF) and a shift of the channel’s inactivation curve
were evident (1).
A complex phenotype like that of the entla mouse is unlikely to be explained by an
altered function of the product of the mutated gene alone. Rather, secondary and
tertiary changes in the expression and/or function of other gene products may be
partially responsible for pathological alterations in neuronal network function. In the
brain of the entla mouse, the mutation of the calcium channel subunit gene Cacna2d2
leads to a pronounced shift in the expression of subunits of several ligand-gated ion
channels that might be involved in the epileptic pathogenesis in this mouse model.
Literature
(1) Brill, J., Klocke, R., Paul, D., Boison, D., Gouder, N., Klugbauer, N., Hofmann, F.,
Becker, C.-M., Becker, K. (2004) Entla: A novel epileptic and ataxic Cacna2d2 mutant of
the mouse. J. Biol. Chem. 279, 7322-7330.
contact:
Stephan Hupfer
University Erlangen-Nuremberg
Institute of Biochemistry
stephan.hupfer@biochem.uni-erlangen.de
Fahrstr. 17
91054 Erlangen (Germany)
additional information
SH acknowledges support by the IZKF Erlangen
JB is now at the Department of Neurology and Neurological Sciences, Stanford University School of
Medicine, Stanford, California 94305, USA