Postnatal liver growth and regeneration are independent of c-myc in a mouse model of conditional hepatic c-myc deletion

Jennifer A Sanders,Ajay Patel,Christoph Schorl,John M Sedivy,Philip A Gruppuso

doi:10.1186/1472-6793-12-1

Jennifer A Sanders, Ajay Patel + Show 3 more

Open Access

https://doi.org/10.1186/1472-6793-12-1

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Abstract

BackgroundThe 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.ResultsLiver 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/fl;Alb-Cre animals. There was also no effect of reducing c-myc on recovery of liver mass following 2/3 partial hepatectomy.Conclusionsc-Myc appears to be dispensable for normal liver growth during the postnatal period, restoration of liver mass following partial hepatectomy and recovery from fasting.

Highlights

The transcription factor c-myc regulates genes involved in hepatocyte growth, proliferation, metabolism, and differentiation
Considered an immediate early gene, c-myc expression is induced within 30 minutes following partial hepatectomy and has been suggested to be a key factor in the transcriptional response leading to the progression of hepatocytes from G0/G1 to S phase [11]
While these studies support a role for c-Myc in hepatocyte growth, ribosomal biogenesis and metabolism, they do not address whether c-Myc is required or whether the effects on these processes were due to superphysiological levels of c-Myc

Summary

Introduction

The transcription factor c-myc regulates genes involved in hepatocyte growth, proliferation, metabolism, and differentiation It has been assigned roles in liver development and regeneration. C-Myc has been shown to regulate genes involved in ribosomal biogenesis, protein translation and the transition from the G0/ G1 to S-phase of the cell cycle suggesting that c-Myc c-Myc has been implicated as a regulator of hepatocyte proliferation, growth and metabolism [8,9]. Other studies involving c-myc transgenic mice have shown that overexpression of cMyc in the liver induces hepatic glucose uptake and utilization and can inhibit gluconeogenesis [13,14] While these studies support a role for c-Myc in hepatocyte growth, ribosomal biogenesis and metabolism, they do not address whether c-Myc is required or whether the effects on these processes were due to superphysiological levels of c-Myc

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