A genetic mouse model of cerebral malformation

In humans, neuronal migration disorders mainly affect the development of cerebral cortex. Clinical features, which depend on the severity of the malformation, include developmental delay, mental retardation, and epilepsy. Furthermore, cortical malformations are a frequent cause of drug-resistant seizures. At present, there are few animal models of cortical malformations and chronic epilepsy. The topic of our research is to characterize a new animal model of cerebral cortex malformation associated with developmental delay and epileptic seizures that appeared spontaneously in our colony, referred to as  the HeCo mouse mutant. The HeCo phenotype is characterized by a heterotopic band of neurons located bilaterally beneath the dorsal part of the neocortex and extends from the frontal to the occipital lobe (see figure). This band is surrounded by white matter that separates it from homotopic cortex above and subcortical structures beneath. We have confirmed that the HeCo mutant trait is transmitted in an autosomal recessive fashion, and genotyping is currently underway. We have two principal aims. First, to investigate the cortical formation in mutant animals by means of live imaging and immunohistochemistry. Second, to determine the tendency to epilepsy by using both EEG recordings in freely moving animals as well as studying GABA A receptors and GABA cells distribution in mutant animals. 
Combining morphologic, physiologic, and genetic methodologies will allow a better understanding of the role of the mutation in cortical malformation and the development of epilepsy.
This unique model represents a new and rare tool to increase our knowledge regarding neocortical development, and to study chronic epilepsy and drug resistance.