title: Loss of zebrafish lgi1b leads to hydrocephalus and sensitization to pentylenetetrazol induced seizure-like behavior.
abstract: Mutations in the LGI1 gene predispose to a hereditary epilepsy syndrome and is the first gene associated with this disease which does not encode an ion channel protein. In zebrafish, there are two paralogs of the LGI1 gene, lgi1a and lgi1b. Knockdown of lgi1a results in a seizure-like hyperactivity phenotype with associated developmental abnormalities characterized by cellular loss in the eyes and brain. We have now generated knockdown morphants for the lgi1b gene which also show developmental abnormalities but do not show a seizure-like behavior. Instead, the most striking phenotype involves significant enlargement of the ventricles (hydrocephalus). As shown for the lgi1a morphants, however, lgi1b morphants are also sensitized to PTZ-induced hyperactivity. The different phenotypes between the two lgi1 morphants support a subfunctionalization model for the two paralogs.
authors: GHSU Cancer Center, School of Medicine, Georgia Health Sciences University, Augusta, Georgia, United States of America.
authors: Yong
authors: Y
authors: Teng
authors: Xiayang
authors: X
authors: Xie
authors: Steven
authors: S
authors: Walker
authors: Meera
authors: M
authors: Saxena
authors: David J
authors: DJ
authors: Kozlowski
authors: Jeff S
authors: JS
authors: Mumm
authors: John K
authors: JK
authors: Cowell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006849:Hydrocephalus / Q000150:complications* / Q000196:embryology / Q000473:pathology*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D010433:Pentylenetetrazole; D010641:Phenotype; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D022821:RNA Splice Sites / Q000235:genetics; D012640:Seizures / Q000150:complications* / Q000196:embryology / Q000473:pathology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: C570207:Lgi1b protein, zebrafish; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D022821:RNA Splice Sites; D029961:Zebrafish Proteins; D010433:Pentylenetetrazole