Major research fields
Behavioral phenotypes are the outcome of integration of complicated neural activities that are affected by genetic and environmental factors. In this laboratory, the neural mechanisms regulating mouse behavioral phenotypes are studied at the molecular, cellular and system level. At this moment, we are focusing on several mouse behaviors affected by ubiquitin specific peptidase 46 (Usp46) that was identified as the gene responsible for reductions in time spent immobile in the tail suspension and forced swim test. Mice with this mutation exhibit a number of impaired behavioral phenotypes including circadian rhythms, maternal behavior and emotional behavior etc. It is thought that Usp46 deficiency causes dysfunction of GABAergic (gamma-aminobutyric acid) system. Specific topics of this laboratory, therefore, are (1) Cellular mechanism: comprehensive analysis of genes and proteins expression in the brain to identify the substrate of USP46 deubiqutinating enzyme. (2) Animal model for human child abuse: to gain insight into the neural mechanism of chills abuse, we utilize Usp46 mutant mice as an animal model for human child abuse because maternal behaviors of these mice are very similar to those of maltreating human mothers. (3) Circadian rhythms: circadian rhythm of Usp46 mutant mice is different from normal mice (e.g. longer circadian period and entrainment to feeding cycles). To know how Usp46 affects circadian rhythms, we study the function of this gene in the regulation of circadian rhythms because abnormality of circadian rhythms is related to human mental disorders.
Major relevant publications
- Ono H, Hoshino Y, Yasuo S, Watanabe M, Nakane Y, Murai A, Ebihara S, Korf HW, Yoshimura T. Involvement of thyrotropin in photoperiodic signal transduction in mice.Proc Natl Acad Sci U S A. 105(47):18238-42, 2008
- Tomida S, Mamiya T, Sakamaki H, Miura M, Aosaki T, Masuda M, Niwa M, Kameyama T, Kobayashi J, Iwaki Y, Imai S, Ishikawa A, Abe K, Yoshimura T, Nabeshima T, Ebihara S. Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests. Nat Genet.41:688-695, 2009.
- Imai S, Mamiya T, Tsukada A, Sakai Y, Mouri A, Nabeshima T, Ebihara S. Ubiquitin-Specific Peptidase 46 (Usp46) Regulates Mouse Immobile Behavior in the Tail Suspension Test through the GABAergic System. PLoS One. 2012;7(6):e39084.
- Imai S, Kano M, Nonoyama K, Ebihara S. Behavioral characteristics of ubiquitin-specific peptidase 46-deficient mice. PLoS One.2013;8(3):e58566.
- Umemura S, Imai S, Mimura A, Fujiwara M, Ebihara S. Impaired maternal behavior in Usp46 mutant mice: a model for trans-generational transmission of maternal care. PloS One,(2015, in press)