result of a mutation in hamsters. the tau mutation in the syrian golden hamster was the first to show a heritable abnormality of circadian rhythms in mammals. hamsters with the mutation exhibit a shorter period than the wild-type. heterozygotes have a period of about 22h while the period of homozygotes is even shorter, at about 20h. because of previous research indicating the role of dbt in establishing period, the tau mutation was found to be at the same locus as the ckiε gene. thus, this mutation relates to the mutations dbts and dbtl, which both effect the internal period of the fly. however, it seems that the forces driving these changes in period are different. it was found that the point mutation resulting in the tau mutant decreased the activity of the ckiε kinase in vitro. in flies, on the other hand, the dbtl mutation is associated with a decrease in dbt activity and a longer period. this is consistent with another experiment done on hamsters that showed a lengthening of the period caused by cki inhibition. to investigate this discrepancy, researchers studied the half-life of per2 under the influence of wild-type ckiε, ckiεtau, and ckiε (k38a) which is a kinase-inactive mutant. the results indicated that the tau mutation was actually a gain-of-function mutation, instead of loss-of-function, that caused the more rapid degradation of the per proteins. therefore, the tau mutation in hamsters can be seen as similar to mutations in dbt that change the internal period. importance of rhythmic phosphorylation a role of ckiε has also been seen in humans related to familial advanced sleep phase syndrome, in which individuals have a much shorter period than the typical human. in this case, it does not seem to be a mutation of the ckiε protein itself, but instead in the binding site for phosphorylation of the per2 protein. in addition, kinase activity has been shown to be involved in the nuclear localization of per and other genes involved in circadian rhythmicity. therefore, it is this phosphorylation that allows per to repress its own transcription and place a delay on the circadian system. without the phosphorylation of per, by dbt in drosophila or by ckiε in mammals, there would be no oscillations because the feedback loop would be broken. it has even been proposed that this rhythmic phosphorylation itself might be a driving factor of circadian clocks. up to this point, the transcription-translation negative feedback loop has been identified as the source of oscillations and rhythms in biological clocks. but, experiments with phosphorylation of the cyanobacterial protein kaic in vitro showed that rhythms persisted without the presence of any transcription or translation. therefore, kinases like dbt and ckiε might play even more important roles within circadian clocks than just targeting proteins for degradation.