Quantitative trait locus analysis of abnormal circadian period in CS mice

CS mice show a free-running period (tau) longer than 24 h and rhythm splitting in constant darkness (DD). These features in behavioral circadian rhythms are distinctive as compared with other inbred strains of mice, which exhibit robust free-running rhythms with tau shorter than 24 h. To identify the genes affecting tau, quantitative trait locus (QTL) analysis was initially conducted by using 289 F-2 mice derived from a cross between CS and C57BL/6J strain. A suggestive QTL (LOD = 3.71) with CS allele increasing tau was detected on the distal region of Chromosome (Chr) 19. Next, using 192 F-2 mice from a cross between CS and MSM strain, the presence of the QTL on Chr 19 was examined, and we confirmed the QTL at the genome-wide significant level (LOD = 4.61 with 10.4% of the total variance explained). This QTL was named long free-running period (Lfp). Three other suggestive QTLs (LOD = 3.24-4.28) were mapped to the midportion of Chr 12 in (CSxC57BL/6J)F-2 mice, and to the proximal and middle region of Chr 19 in (CSxMSM)F-2 mice, respectively, of which, CS alleles for two QTLs on Chr 19 have the effect of lengthening tau. None of these QTLs were mapped to the chromosomal regions of previously described QTLs for tau and known clock genes (Clock, mPer1, Bmal1, mCry1, mCry2, mTim, and Csnk1e).