RT Journal Article
SR Electronic
T1 A Genetic Animal Model of Human Neocortical Heterotopia Associated with Seizures
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6236
OP 6242
DO 10.1523/JNEUROSCI.17-16-06236.1997
VO 17
IS 16
A1 Kevin S. Lee
A1 Frank Schottler
A1 Jennifer L. Collins
A1 Giuseppe Lanzino
A1 Daniel Couture
A1 Anand Rao
A1 Ken-ichiro Hiramatsu
A1 Yasunobu Goto
A1 Seung-Chyul Hong
A1 Hakan Caner
A1 Haruaki Yamamoto
A1 Zong-Fu Chen
A1 Edward Bertram
A1 Stuart Berr
A1 Reed Omary
A1 Heidi Scrable
A1 Theodore Jackson
A1 John Goble
A1 Leonard Eisenman
YR 1997
UL http://www.jneurosci.org/content/17/16/6236.abstract
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 thetish 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 thetish 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.