%0 Journal Article
%T Effect of chronic ethanol exposure on the liver of Clock-mutant mice
%A Takashi Kudo
%A Toru Tamagawa
%A Shigenobu Shibata
%J Journal of Circadian Rhythms
%D 2009
%I BioMed Central
%R 10.1186/1740-3391-7-4
%X In humans, chronic ethanol consumption leads to a characteristic set of changes to the metabolism of lipids in the liver that is referred to as an "alcoholic fatty liver" (AFL) [1]. This condition is characterized by an increase in liver weight [2], the accumulation of triglycerides and changes in expression of genes involved in lipid metabolism [3]. In severe cases, these changes eventually lead to inflammation [4] and steatohepatitis [5] and are considered risk factors for cirrhosis and liver cancer in humans. Most of these changes are also observed in rodents [6] allowing us to use chronic alcohol exposure in rodents as a model to understand the human condition.In recent years, many of the genes responsible for the generation of circadian rhythms have been identified [7]. Many of these genes have been found to be expressed in the liver where the transcription of a number of key genes is regulated on a circadian time scale [8]. Mice containing a mutation in the transcription factor, CLOCK, are unable to generate circadian rhythms in behavior and hepatic gene expression [9,10]. Interestingly, recent studies suggest that Clock-mutant mice exhibit abnormal triglycerides [11], cholesterol metabolism [12], and become obese [13]. Therefore, to understand the potential interactions between ethanol consumption, lipid metabolism and the circadian clock, we investigated the effect of chronic ethanol intake on the lipid metabolism of Clock-mutant mice.Clock-mutant mice were purchased from The Jackson Laboratory (stock no. 002923, Bar Harbor, ME). These mice, originally with the Clock allele on a C57BL/6J background, were backcrossed using a Jcl: ICR background more than eight generations. We placed them in the ICR genetic background to enhance the robustness of the breeding and care of the young. Other groups have reported that the Clock-mutant mice with a C57BL/6J background died in their infancy because the dams did not care for them [14-16]. Clock-mutant mice were heteroz
%U http://www.jcircadianrhythms.com/content/7/1/4