[Identification of a gene regulating "behavioral despair" in mice].

We found that CS mice exhibit an extremely low immobility time (almost no immobility) in both the tail suspension test (TST) and forced swimming test (FST). In these tests, animals are subjected to the short-term, inescapable stress of being suspended by their tail or being forced to swim in a water-filled cylinder. In such situations, the animals rapidly adopt a characteristic immobile posture that has been named "behavioral despair" on the assumption that the animals have given up hope of escaping.

Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests.

The tail suspension test (TST) and forced swimming test (FST) are widely used for assessing antidepressant activity and depression-like behavior. We found that CS mice show negligible immobility in inescapable situations. Quantitative trait locus (QTL) mapping using CS and C57BL/6J mice revealed significant QTLs on chromosomes 4 (FST) and 5 (TST and FST).

Genetic and molecular analysis of wild-derived arrhythmic mice.

A new circadian variant was isolated by screening the intercross offspring of wild-caught mice (Mus musculus castaneus). This variant was characterized by an initial maintenance of damped oscillations and subsequent loss of rhythmicity after being transferred from light-dark (LD) cycles to constant darkness (DD). To map the genes responsible for the persistence of rhythmicity (circadian ratio) and the length of free-running period (tau), quantitative trait locus (QTL) analysis was performed using F(2) mice obtained from an F(1) cross between the circadian variant and C57BL/6J mice.

Peripheral clock gene expression in CS mice with bimodal locomotor rhythms.

CS mice show unique properties of circadian rhythms: unstable free-running periods and distinct bimodal rhythms (similar to rhythm splitting, but hereafter referred to as bimodal rhythms) under constant darkness. In the present study, we compared clock-related gene expression (mPer1, mBmal1 and Dbp) in the SCN and peripheral tissues (liver, adrenal gland and heart) between CS and C57BL/6J mice. In spite of normal robust oscillation in the SCN of both mice, behavioral rhythms and peripheral rhythms of clock-related genes were significantly different between these mice.