postnatal liver growth and regeneration are independent of c-myc in a mouse model of conditional hepatic c-myc deletion产后肝脏生长和再生是独立的原癌基因的小鼠模型条件肝原癌基因的删除.pdfVIP

Sanders et al. BMC Physiology 2012, 12:1 /1472-6793/12/1 RESEARCH ARTICLE Open Access Postnatal liver growth and regeneration are independent of c-myc in a mouse model of conditional hepatic c-myc deletion 1* 2,3 4 2,3 1,2 Jennifer A Sanders , Christoph Schorl , Ajay Patel , John M Sedivy and Philip A Gruppuso Abstract Background: The transcription factor c-myc regulates genes involved in hepatocyte growth, proliferation, metabolism, and differentiation. It has also been assigned roles in liver development and regeneration. In previous studies, we made the unexpected observation that c-Myc protein levels were similar in proliferating fetal liver and quiescent adult liver with c-Myc displaying nucleolar localization in the latter. In order to investigate the functional role of c-Myc in adult liver, we have developed a hepatocyte-specific c-myc knockout mouse, c-mycfl/fl;Alb-Cre. Results: Liver weight to body weight ratios were similar in control and c-myc deficient mice. Liver architecture was unaffected. Conditional c-myc deletion did not result in compensatory induction of other myc family members or in c-Myc’s binding partner Max. Floxed c-myc did have a negative effect on Alb-Cre expression at 4 weeks of age. To explore this relationship further, we used the Rosa26 reporter line to assay Cre activity in the c-myc floxed mice. No significant difference in Alb-Cre activity was found between control and c-mycfl/fl mice. c-myc deficient mice were studied in a nonproliferative model of liver growth, fasting for 48 hr followed by a 24 hr refeeding period. Fasting resulted in a decrease in liver mass and liver protein, both of which recovered upon 24 h of refeeding in the c-mycfl/