Orthologs of Drosophila pointed and Arginine kinase 1 impact sleep in mice.

Abstract

Model organisms such as Drosophila are powerful tools to study the genetic basis of sleep. Previously, we identified the genes pointed and Arginine kinase 1 using selective breeding for long and short sleep duration in an outbred population of Drosophila. pointed is a transcription factor that is part of the epidermal growth factor receptor signaling pathway, while Arginine kinase 1 is involved in proline and arginine metabolism. Conserved orthologs of these genes exist in mice, leading us to hypothesize that they would also impact sleep in a murine model. We generated mutations in the murine orthologs Ets1 and Ckm using CRISPR in a C57BL/6N background and used video analysis to measure sleep in the mice. Both mutations affected sleep parameters, and the effects were observed predominantly in female mice, with males showing fewer differences from littermate controls. The study of natural populations in flies therefore leads to candidate genes with functional conservation on sleep in mammals.