GSE173885
Transcriptome of the audiogenic rat strain and identification of possible audiogenic epilepsy-associated genes
Audiogenic epilepsy (AE), developing in rodent strains in response to loud sound, is widely used as the model of generalized convulsive epilepsy. The molecular and genetic mechanisms that determine the expression of AE are currently non well understood. In the present work we compared transcriptomes from the inferior and superior colliculi (corpora quadrigemina), the crucial epileptogenic midbrain zone for AE in order to identify genes associated to the AE phenotype. Transcriptomes of rats from three strains were compared: Krushinsky-Molodkina (KM) strain (100% AE-prone); Wistar outbred rats (with no AE proneness) and "0" strain, selected from F2 KMxWistar hybrids for the lack of AE. It is shown that KM strain gene expression profile have a number of characteristic differences from those of Wistar and "0" strains. In particular, KM has increased expression of a number of genes involved in positive regulation of the MAPK signaling cascade, as well as genes, responsible for positive regulation of apoptotic processes. The next characteristic difference between the KM strain from Wistar and "0" is a multiple increase in the expression level of the Ttr gene, which is known to be associated with family amyloid polyneuropathy in humans. Further, the KM strain showed a significant decrease in the expression of the Msh3 gene involved in the DNA mismatch repair system, Acsm5, coding a mitochondrial acyl-CoA synthetase specific for medium chain family member 5, and in a number of genes of the oxidative phosphorylation system, and a number of some other genes. Our data confirm the complex multigenic nature of AE inheritance in rodents. A comparison with the data obtained from other AE rodent strains suggests that the convulsive phenotype could develop differently in audiogenic rat strains selected independently. Although, the finding of parallel differences in certain genes expression in AE-prone hamsters (another rodent species) indicate the common (and crucial) neurogenetic defects, leading to AE phenotype in rodents in general. Overall design: KM - audiogenic epilepsy rat strain; W - wistar control rat strain; 0 - outbred strain from KM rats