ZFIN ID: ZDB-PUB-111117-19
Loss of Zebrafish lgi1b Leads to Hydrocephalus and Sensitization to Pentylenetetrazol Induced Seizure-Like Behavior
Teng, Y., Xie, X., Walker, S., Saxena, M., Kozlowski, D.J., Mumm, J.S., and Cowell, J.K.
Date: 2011
Source: PLoS One   6(9): e24596 (Journal)
Registered Authors: Kozlowski, David J., Mumm, Jeff, Saxena, Meera T., Walker, Steven, Xie, Xiayang
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Behavior, Animal*
  • Brain/drug effects
  • Brain/growth & development
  • Brain/pathology
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Hydrocephalus/complications*
  • Hydrocephalus/embryology
  • Hydrocephalus/pathology*
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Nerve Tissue Proteins/chemistry
  • Nerve Tissue Proteins/deficiency*
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Pentylenetetrazole
  • Phenotype
  • Proto-Oncogene Proteins c-fos/metabolism
  • RNA Splice Sites/genetics
  • Seizures/complications*
  • Seizures/embryology
  • Seizures/pathology
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/deficiency*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 22053218 Full text @ PLoS One

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.