Increased seizure susceptibility and cortical malformation in beta-catenin mutant mice.
Beta-catenin has been implicated in epilepsy because of its altered post seizure expression and the role of Wnt2 signaling in autism. To determine beta-catenin's role in seizure susceptibility, we injected penetylenetetrazol intraperitoneally in beta-catenin cerebral cortex- and hippocampus-specific knockout mice. We then analyzed the latency, number, and duration of four phases of seizure behaviors: (I) non-seizure activity, (II) myoclonic jerks, (III) generalized clonic seizures, and (IV) tonic seizures. The latencies to both death and Phase IV were significantly reduced in mutant mice. Mutant mice also spent significantly more time in Phases III and IV and showed significantly less time in the non-convulsive state (Phase I). Nissl and gold chloride staining indicated that the knockout mice had underdeveloped cortices, lacked a corpus callosum, and were missing hippocampal structures. This suggests that dysfunction of beta-catenin-mediated signaling pathways in mice leads to cortical malformation and increased seizure susceptibility.
Campos
Victor E
VE
NeuroTech Group, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Du
Mengyuan
M
Li
Yuqing
Y
D000818:Animals; D001483:Base Sequence; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D020022:Genetic Predisposition to Disease; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D012640:Seizures / Q000235:genetics*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D015534:Trans-Activators; D051176:beta Catenin