Exploring novel genetic factors involved in sleep/wake regulation using inter-subspecific consomic strains established from MSM/Ms and C57BL/6J mice

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Comprehensive phenotypic analysis was performed in B6-Chr5CMSM (5C)and B6-Chr5TMSM (5T), a consomic strain with 1-45cM and 41-86cM segments of chromosome5 from MSM on a B6 background, respectively. Their parental strains, C57BL/6J (B6), a commonly used laboratory mouse strain, and MSM, a wild-derived inbred mouse strain whose genetic background is diverse from that of B6, were analyzed in parallel. MSM chromosome5 in the context of a B6 genetic background conferred distinct differences in phenotypesfrom B6 controls. 5C had more consolidated sleep than B6. 5T had three distinct differences from B6 that can be summarized as follows: 1) The longest wake duration of 5T was 2.6times longer than that of B6; 2) Theta peak frequency (TPF) during rapid eye movementsleep in 5T was significantly lower than that in B6; 3) 5T showed occasional (up to 19 events in 30 min) spontaneous electroencephalogram (EEG) discharges lasting around 1second, which was not observed in B6. The amplitude of such EEG discharges was twice ashigh as that of the normal waking EEG level with a peak frequency of 6-8Hz. In order to examine the hereditary patterns of these three phenotypes identified between B6 and 5T,sleep/wake in (B6×5T)F1 was analyzed and the results were compared with that of B6 and5T. As a result, (B6×5T)F1 had B6-like phenotypes in terms of TPF and EEG dischargefrequency. Therefore, in the next step, linkage analysis was performed using{(B6×5T)F1×5T}N2. As a result, the genetic region associated with both the longest wake duration and EEG discharges was suggested to be located around D5Mit338 (59cM), and that associated with TPF to be located around D5Mit338 (59cM) and/or D5Mit141 (74cM).