Overexpression of the IGF2-mRNA binding protein p62 in transgenic mice induces a steatotic phenotype

J Hepatol. 2011 May;54(5):994-1001. doi: 10.1016/j.jhep.2010.08.034. Epub 2010 Oct 26.


Background & aims: The insulin-like growth-factor 2 (IGF2) mRNA binding protein p62 is highly expressed in hepatocellular carcinoma tissue. Still, its potential role in liver disease is largely unknown. In this study, we investigated pathophysiological implications of p62 overexpression in mice.

Methods: We generated mice overexpressing p62 under a LAP-promotor. mRNA expression levels and stability were examined by real-time RT-PCR. Allele-specific expression of Igf2 and H19 was assessed after crossing mice with SD7 animals. The Igf2 downstream mediators pAKT and PTEN were determined by Western blot.

Results: Hepatic p62 overexpression neither induced inflammatory processes nor liver damage. However, 2.5week old transgenic animals displayed a steatotic phenotype and improved glucose tolerance. p62 overexpression induced the expression of the imprinted genes Igf2 and H19 and their transcriptional regulator Aire (autoimmune regulator). Neither monoallelic expression nor mRNA stability of Igf2 and H19 was affected. Investigating Igf2 downstream signalling pathways showed increased AKT activation and attenuated PTEN expression.

Conclusions: The induction of a steatotic phenotype implies that p62 plays a role in hepatic pathophysiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Gene Expression / physiology
  • Glucose Intolerance / genetics
  • Glucose Intolerance / metabolism
  • Glucose Intolerance / pathology
  • Humans
  • Insulin-Like Growth Factor II / genetics*
  • Liver / pathology*
  • Liver / physiology
  • Mice
  • Mice, Transgenic
  • Non-alcoholic Fatty Liver Disease
  • Phenotype
  • Promoter Regions, Genetic / physiology
  • RNA, Messenger / metabolism
  • Transcription Factor TFIIH
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Gtf2h1 protein, mouse
  • IGF2 protein, mouse
  • RNA, Messenger
  • Transcription Factors
  • Transcription Factor TFIIH
  • Insulin-Like Growth Factor II