Putative causal variant on Vlgr1 for the epileptic phenotype in the model wistar audiogenic rat.
No Thumbnail Available
Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Wistar Audiogenic Rat is an epilepsy model whose animals are predisposed to develop
seizures induced by acoustic stimulation. This model was developed by selective
reproduction and presents a consistent genetic profile due to the several generations
of inbreeding. In this study, we performed an analysis of WAR RNA-Seq data, aiming
identified at genetic variants that may be involved in the epileptic phenotype. Seventeen
thousand eighty-five predicted variants were identified as unique to the WAR model,
of which 15,915 variants are SNPs and 1,170 INDELs. We filter the predicted variants
by pre-established criteria and selected five for validation by Sanger sequencing. The
genetic variant c.14198T>C in the Vlgr1 gene was confirmed in the WAR model.
Vlgr1 encodes an adhesion receptor that is involved in the myelination process, in
the development of stereocilia of the inner ear, and was already associated with the
audiogenic seizures presented by the mice Frings. The transcriptional quantification of
Vlgr1 revealed the downregulation this gene in the corpus quadrigeminum of WAR, and
the protein modeling predicted that the mutated residue alters the structure of a domain
of the VLGR1 receptor. We believe that Vlgr1 gene may be related to the predisposition
of WAR to seizures and suggest the mutation Vlgr1/Q4695R as putative causal variant,
and the first molecular marker of the WAR strain.
Description
Keywords
Seizure predisposition, Mutation, Sequencing, Molecular marker
Citation
DAMASCENO, S. et al. Putative causal variant on Vlgr1 for the epileptic phenotype in the model wistar audiogenic rat. Frontiers in Neurology, v. 12, 2021. Disponível em: <https://www.frontiersin.org/articles/10.3389/fneur.2021.647859/full>. Acesso em: 11 out. 2022.