the "fbxl3" gene function was independently identified in 2007 by three groups lead by michele pagano, joseph s. takahashi, dr. patrick nolan and michael hastings, respectively. takahashi used forward genetics n-ethyl-n-nitrosourea (enu) mutagenesis to screen for mice with varied circadian activity which led to the discovery of the "overtime" ("ovtm") mutant of the "fbxl3" gene. nolan discovered the "fbxl3" mutation "after hours" ("afh") by a forward screen assessing wheel activity behavior of mutagenized mice. the phenotypes identified in mice were mechanistically explained by pagano who discovered that the fbxl3 protein is necessary for the reactivation of the clock and bmal1 protein heterodimer by inducing the degradation of cry proteins.