The Might of Mice in Advancing Sleep Genetics

Forward and reverse genetic approaches in simpler animal models, including zebrafish, flies, and worms, have greatly accelerated sleep gene discovery. Yet, the mouse remains as an indispensable and complimentary model in sleep genetics. Murine models are used to confirm and specify further the role(s) of a gene identified in simpler animal models plays in mammalian sleep. As we now appreciate the importance of specific sleep state-specific electrographic waveforms in the consolidation of memories, mouse models play critical roles in characterizing gene effects on electrographic phenomena in sleep. At the same time, newer strategies in forward genetics in the mouse have identified both dominant and recessive genes influencing sleep. To date, diverse families of genes, from ion channel subunit genes to genes regulating circadian rhythms, metabolism, and inflammation, have been shown to influence sleep in the mouse. Human genome wide association studies have identified genetic loci associated with specific sleep disorders, and the mouse has been indispensable in establishing the roles of putative sleep genes identified in human studies. Armed with novel genetic tools and approaches coupled with advancements in our understanding of the role of sleep in memory and brain health, we are well-poised to more fully realize the might of the mouse in advancing the genetics of sleep.