Genetic mechanisms underlying abnormal neuronal migration in classical lissencephaly.
Classical lissencephaly is a human developmental brain disorder characterized by a paucity of cortical gyration and thickening of the cortical gray matter, leading to severe epilepsy and mental retardation. Loss-of-function mutations in the microtubule-associated protein encoding genes, PAFAH1B1 (encoding the protein LIS1), DCX and TUBA1A have been implicated in the pathogenesis of the condition. Animal models are required to understand the basis of this disease, which is a challenge, given that mice normally have a smooth cortex. Recent advances toward this goal have come from stepwise reduction in gene function, deletion of redundant genes and acute gene inactivation using short hairpin RNA (shRNA). These approaches have implicated genes that regulate the microtubule cytoskeleton during neuronal division, migration and maturation.
Kerjan
Geraldine
G
Neurogenetics Laboratory, Department of Neurosciences, LBR3A16, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0691, USA.
Gleeson
Joseph G
JG
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics; D000818:Animals; D002465:Cell Movement; D002540:Cerebral Cortex / Q000002:abnormalities / Q000196:embryology; D003598:Cytoskeletal Proteins / Q000235:genetics; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019143:Evolution, Molecular; D006801:Humans; D054082:Lissencephaly / Q000196:embryology* / Q000235:genetics* / Q000473:pathology; D054081:Malformations of Cortical Development, Group II / Q000235:genetics*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008954:Models, Biological; D009154:Mutation; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics
D003598:Cytoskeletal Proteins; C000714328:DCX protein, human; C482331:DNMBP protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human