A quantitative genetic analysis of slow-wave sleep in influenza-infected CXB recombinant inbred mice

Influenza-infected 57BL/6J mice spend increased amounts of time in slow-wav e sleep (SWS) during the dark phase of the circadian cycle compared to heal thy mice. In contrast, infected BALB/cByJ mice show a normal or reduced tim e in SWS, particularly during the light phase. To identify genetic loci wit h linkage to these traits, we measured sleep in 13 CXB recombinant inbred ( RI) strains derived from a cross between C57BL/6ByJ and BALB/cByJ mice. The probability density distribution of sleep patterns of influenza-infected C XB RI mice showed modes that correspond roughly with the parental modes dur ing the dark phase of the circadian cycle and are intermediate or C57BL/6-l ike during the light phase. These patterns are consistent with the presence of a low number of major effect quantitative trait loci (QTLs). Chromosoma l regions with provisional association to strain variation in influenza-ind uced SWS patterns were identified. In particular, a 10- to 12-cM interval o n Chr 6 between D6Mit74 and D6Mit188 contains a QTL (LRS = 16.6 at 1 cM pro ximal to D6Mit316; genomewide p < .05) that influences the SWS response to influenza infection during the light phase. We have provisionally named thi s QTL Srilp1 (sleep response to influenza, light phase 1). Candidate genes for mediation of this phenotype include Ghrhr (growth hormone releasing hor mone receptor), Crhr2 (corticotropin releasing hormone receptor 2), and Cd8 a (an epitope on cytotoxic T lymphocytes). Several other intervals achieved suggestive probability scores that are sufficient to warrant further analy sis either with additional RI strains or with F-2 panels. The analysis also suggests that dark phase and light phase responses are regulated by differ ent genetic factors.