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PMID:19624305

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Citation

Frankel, WN, Yang, Y, Mahaffey, CL, Beyer, BJ and O'Brien, TP (2009) Szt2, a novel gene for seizure threshold in mice. Genes Brain Behav. 8:568-76

Abstract

In a chemical mutagenesis screen we identified Szt2 (seizure threshold 2) as a gene that confers low seizure threshold to mice and may also enhance epileptogenesis. The semidominant phenotype was mapped to Chromosome 4 and narrowed further to a critical interval of approximately 650 kb. A novel large (> 10 kb) transcript in the critical interval was found to have fourfold increased steady-state expression at the RNA level in Szt2 homozygous mutant brain. The corresponding 72 exon gene encodes a 378-kD protein with no significant or suggestive sequence similarities to any other protein. The mutant allele of Szt2 contains a splice donor mutation after exon 32, predicting transcriptional read-through, translational frameshift and premature stop. A second Szt2 allele, containing a gene-trap mutation in exon 21, also conferred a low seizure threshold and increased RNA expression, but unlike the original allele, some gene-trap homozygotes died embryonically. Szt2 is transcribed in many tissues, with the highest expression in brain, and it is also expressed during embryonic development. Szt2 is highly conserved in evolution, with a clear, single orthologue found in all land vertebrates and in many invertebrates. Interestingly, in mammals the Szt2 gene resides in a highly conserved head-to-head configuration with Med8 (which encodes a Mediator complex subunit), separated by only 91 nt. While the biological function of Szt2 remains unknown, its high conservation, unique structure and effect on seizure threshold suggest that it serves an important role in the central nervous system.

Links

PubMed PMC2728062 Online version:10.1111/j.1601-183X.2009.00509.x

Keywords

Amino Acid Sequence; Animals; Base Sequence; Brain/metabolism; Brain/physiopathology; Brain Chemistry/genetics; Cells, Cultured; Chromosome Mapping; Conserved Sequence; Disease Models, Animal; Epilepsy/genetics; Epilepsy/metabolism; Epilepsy/physiopathology; Evolution, Molecular; Exons; Frameshift Mutation/genetics; Genetic Predisposition to Disease/genetics; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/isolation & purification; Nerve Tissue Proteins/metabolism; RNA, Messenger/analysis; RNA, Messenger/metabolism; Sequence Homology, Amino Acid

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SZT2

acts_upstream_of_or_within

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4353996

P

Seeded From UniProt

complete

MOUSE:SZT2

acts_upstream_of_or_within

GO:0009791: post-embryonic development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4353996

P

Seeded From UniProt

complete

MOUSE:SZT2

acts_upstream_of_or_within

GO:0043473: pigmentation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4353996

P

  • occurs_in:(EMAPA:18769)

Seeded From UniProt

complete


See also

References

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