Transcriptome analysis of Inbred Long Sleep and Inbred Short Sleep mice

• Published in: Genes, brain and behavior brain and behavior, 2013-03, Vol.12 (2), p.263-274
• Main Authors: Darlington, T. M., Ehringer, M. A., Larson, C., Phang, T. L., Radcliffe, R. A.
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Alcohol; Alcoholism; Animals; Biological and medical sciences; Brain; Brain - metabolism; Cufflinks; DNA microarrays; Dopamine and cAMP-Regulated Phosphoprotein 32 - genetics; Enkephalins - genetics; Enkephalins - metabolism; eQTL; Ethanol; Ethanol - pharmacology; Exome; Gene expression; Gene Expression Profiling; Gene polymorphism; Gene Regulatory Networks; Genes; High-Throughput Nucleotide Sequencing; Inbred Long Sleep; Inbred Short Sleep; Inbreeding; Kinases; Lore QTL; loss‐of‐righting‐reflex; Male; MAP kinase; Medical sciences; Mice; Mice, Inbred Strains; Myosin; Myosins - genetics; Myosins - metabolism; Neostriatum; Phosphoprotein phosphatase; Polymorphism, Genetic; Potassium channels; Prealbumin - genetics; Prealbumin - metabolism; Prodynorphin; Proenkephalin; Protein Precursors - genetics; Protein Precursors - metabolism; Proteins; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Ras protein; RNA; RNA‐sequencing; Sequence Analysis, RNA; Sleep; Sleep - drug effects; Sleep - genetics; Tophat; Transcription, Genetic - drug effects; Transcription, Genetic - genetics; Transcriptome; transthyretin; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; WGCNA
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/gbb.12018

Many studies have utilized the Inbred Long Sleep and Inbred Short Sleep mouse strains to model the genetic influence on initial sensitivity to ethanol. The mechanisms underlying this divergent phenotype are still not completely understood. In this study, we attempt to identify genes that are differentially expressed between these two strains and to identify baseline networks of co‐expressed genes, which may provide insight regarding their phenotypic differences. We examined the whole brain and striatal transcriptomes of both strains, using next generation RNA sequencing techniques. Many genes were differentially expressed between strains, including several in chromosomal regions previously shown to influence initial sensitivity to ethanol. These results are in concordance with a similar sample of striatal transcriptomes measured using microarrays. In addition to the higher dynamic range, RNA‐Seq is not hindered by high background noise or polymorphisms in probesets as with microarray technology, and we are able to analyze exome sequence of abundant genes. Furthermore, utilizing Weighted Gene Co‐expression Network Analysis, we identified several modules of co‐expressed genes corresponding to strain differences. Several candidate genes were identified, including protein phosphatase 1 regulatory unit 1b (Ppp1r1b), prodynorphin (Pdyn), proenkephalin (Penk), ras association (RalGDS/AF‐6) domain family member 2 (Rassf2), myosin 1d (Myo1d) and transthyretin (Ttr). In addition, we propose a role for potassium channel activity as well as map kinase signaling in the observed phenotypic differences between the two strains. RNA‐Seq of striatal/whole brain transcriptomes of ILS and ISS mice show differences in numerous biological pathways.