Targeted Disruption of the Murine Homeodomain-Interacting Protein kinase-2 Causes Growth Deficiency in Vivo and Cell Cycle Arrest in Vitro

DNA Cell Biol. 2009 Apr;28(4):161-7. doi: 10.1089/dna.2008.0778.


The homeodomain-interacting protein kinase 2 (HIPK2) protein is a member of a recently identified family of nuclear protein kinases that are well conserved in various organisms. HIPK2 can bind to several homeotic factors and to a series of proteins involved in the regulation of cell survival and proliferation in response to morphogenetic and genotoxic signals. Here we report Hipk2-targeted disruption in mouse; Hipk2(-/-) mice are viable and fertile but significantly smaller than their wild-type littermates. This feature is present at birth and retained throughout the mouse adulthood. Mouse embryo fibroblasts from Hipk2(-/-) mice show a reduced proliferation rate, compared to the wild-type counterparts, with accumulation in the G0/G1 phase of the cell cycle and altered levels of the cell cycle regulators cyclin D and CDK6. Restoration of wild-type HIPK2 expression in Hipk2(-/-) cells rescues the normal phenotype supporting a role for HIPK2 in the regulation of cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Body Size / genetics*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle
  • Cell Proliferation*
  • Fertility / genetics*
  • Fibroblasts / cytology
  • Gene Targeting
  • Mice
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*


  • Carrier Proteins
  • Hipk2 protein, mouse
  • Protein-Serine-Threonine Kinases