Nxf and Fbxo33: novel seizure-responsive genes in mice.
Much is understood about the response of the brain to seizure but little is known in relation to the underlying molecular mechanisms involved. We used microarray technology to investigate the complex genetic response of the brain to generalized seizure. For this investigation a seizure-specific mouse brain cDNA library was generated and spotted onto microarray slides with the aim of increasing the likelihood of identifying novel genes responsive to seizure. Microarray analysis was performed on mouse hippocampus 1 h after generalized seizure pharmacologically induced by pentylenetetrazol (PTZ). Using the custom microarray slides, six genes were identified as being up-regulated in this seizure model and results were validated by real-time PCR. Four of the seizure-responsive genes had previously-reported roles in apoptosis, proliferation or differentiation of neural cells. Two of the genes were novel and in situ hybridization analysis demonstrated heightened mRNA expression in the hippocampus 1 h following generalized convulsive seizure, in a pattern which is typical for other activity-dependant genes expressed in this structure. In addition to being up-regulated postseizure, the genes described in this paper appear to be expressed normally in the adult hippocampus and during development.
Flood
Warren D
WD
Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, SA, Australia 5006.
Moyer
Robert W
RW
Tsykin
Anna
A
Sutherland
Grant R
GR
Koblar
Simon A
SA
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000503:physiopathology; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D006624:Hippocampus / Q000502:physiology / Q000503:physiopathology; D017403:In Situ Hybridization; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012016:Reference Values; D012097:Repressor Proteins; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; C494218:Fbxo33 protein, mouse; D009419:Nerve Tissue Proteins; C459540:Nfx1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors