Sep 12, 2019

Deletion of a non-canonical promoter regulatory element causes loss of Scn1a expression and epileptic phenotypes in mice

BioRxiv : the Preprint Server for Biology
Jessica L HaighAlex S Nord


Genes with multiple co-active promoters appear common in brain, yet little is known about functional requirements for these potentially redundant genomic regulatory elements. SCN1A, which encodes the NaV1.1 sodium channel alpha subunit, is one such gene with two co-active promoters. Mutations in SCN1A are associated with epilepsy, including Dravet Syndrome (DS). The majority of DS patients harbor coding mutations causing SCN1A haploinsufficiency, however putative causal non-coding promoter mutations have been identified. To model the functional role of potentially redundant Scn1a promoters, we focused on the non-coding Scn1a 1b regulatory region, previously described as a non-canonical alternative transcriptional start site. Mice harboring deletion of the extended evolutionarily-conserved 1b non-coding interval exhibited surprisingly severe reduction of Scn1a and NaV1.1 expression in brain with accompanying seizures and behavioral deficits. This identified the 1b region as a critical disease-relevant regulatory element and provides evidence that non-canonical and apparently redundant promoters can have essential function.

  • References
  • Citations


  • We're still populating references for this paper, please check back later.
  • References
  • Citations


  • This paper may not have been cited yet.

Mentioned in this Paper

Infantile Severe Myoclonic Epilepsy
NAV1.1 Voltage-Gated Sodium Channel
Transcription, Genetic
Genomic Stability
Gene Deletion
SCN1A gene

About this Paper

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

Epileptic Disorders : International Epilepsy Journal with Videotape
Dena MatalonEric D Marsh
Pediatric Neurology
Radhika DhamijaSuresh Kotagal
Proceedings of the National Academy of Sciences of the United States of America
Rachael E SteinWilliam A Catterall
© 2020 Meta ULC. All rights reserved