TY - JOUR
T1 - A genetic animal model of human neocortical heterotopia associated with seizures
AU - Lee, Kevin S.
AU - Schottler, Frank
AU - Collins, Jennifer L.
AU - Lanzino, Giuseppe
AU - Couture, Daniel
AU - Rao, Anand
AU - Hiramatsu, Ken Ichiro
AU - Goto, Yasunobu
AU - Hong, Seung Chyul
AU - Caner, Hakan
AU - Yamamoto, Haruaki
AU - Chen, Zong Fu
AU - Bertram, Edward
AU - Berr, Stuart
AU - Omary, Reed
AU - Scrable, Heidi
AU - Jackson, Theodore
AU - Goble, John
AU - Eisenman, Leonard
PY - 1997/8/15
Y1 - 1997/8/15
N2 - Malformations of the human neocortex are commonly associated with developmental delays, mental retardation, and epilepsy. This study describes a novel neurologically mutant rat exhibiting a forebrain anomaly resembling the human neuronal migration disorder of double cortex. This mutant displays a telencephalic internal structural heterotopia (tish) that is inherited in an autosomal recessive manner. The bilateral heterotopia is prominent below the frontal and parietal neocortices but is rarely observed in temporal neocortex. Neurons in the heterotopia exhibit neocortical-like morphologies and send typical projections to subcortical sites; however, characteristic lamination and radial orientation are disturbed in the heterotopia. The period of neurogenesis during which cells in the heterotopia are generated is the same as in the normotopic neocortex; however, the cells in the heterotopia exhibit a 'rim-to-core' neurogenetic pattern rather than the characteristic 'inside-out' pattern observed in normotopic neocortex. Similar to the human syndrome of double cortex, some of the animals with the fish phenotype exhibit spontaneous recurrent electrographic and behavioral seizures. The tish rat is a unique neurological mutant that shares several features with a human cortical malformation associated with epilepsy. On the basis of its regional connectivity, histological composition, and period of neurogenesis, the heterotopic region in the tish rat is neocortical in nature. This neurological mutant represents a novel model system for investigating mechanisms of aberrant neocortical development and is likely to provide insights into the cellular and molecular events contributing to seizure development in dysplastic neocortex.
AB - Malformations of the human neocortex are commonly associated with developmental delays, mental retardation, and epilepsy. This study describes a novel neurologically mutant rat exhibiting a forebrain anomaly resembling the human neuronal migration disorder of double cortex. This mutant displays a telencephalic internal structural heterotopia (tish) that is inherited in an autosomal recessive manner. The bilateral heterotopia is prominent below the frontal and parietal neocortices but is rarely observed in temporal neocortex. Neurons in the heterotopia exhibit neocortical-like morphologies and send typical projections to subcortical sites; however, characteristic lamination and radial orientation are disturbed in the heterotopia. The period of neurogenesis during which cells in the heterotopia are generated is the same as in the normotopic neocortex; however, the cells in the heterotopia exhibit a 'rim-to-core' neurogenetic pattern rather than the characteristic 'inside-out' pattern observed in normotopic neocortex. Similar to the human syndrome of double cortex, some of the animals with the fish phenotype exhibit spontaneous recurrent electrographic and behavioral seizures. The tish rat is a unique neurological mutant that shares several features with a human cortical malformation associated with epilepsy. On the basis of its regional connectivity, histological composition, and period of neurogenesis, the heterotopic region in the tish rat is neocortical in nature. This neurological mutant represents a novel model system for investigating mechanisms of aberrant neocortical development and is likely to provide insights into the cellular and molecular events contributing to seizure development in dysplastic neocortex.
KW - Cortical heterotopia
KW - Double cortex
KW - Epilepsy
KW - Neurogenesis
KW - Neuronal migration disorder
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=0030797143&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030797143&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.17-16-06236.1997
DO - 10.1523/jneurosci.17-16-06236.1997
M3 - Article
C2 - 9236234
AN - SCOPUS:0030797143
SN - 0270-6474
VL - 17
SP - 6236
EP - 6242
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 16
ER -