Mice deficient for all PIM kinases display reduced body size and impaired responses to hematopoietic growth factors

H Mikkers, M Nawijn, J Allen, Conny Brouwers, E Verhoeven, Jos Jonkers, A Berns*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

250 Citations (Scopus)

Abstract

The Pim family of proto-oncogenes encodes a distinct class of serine/threonine kinases consisting of PIM1, PIM2, and PIM3. Although the Pim genes are evolutionarily highly conserved, the contribution of PIM proteins to mammalian development is unclear. PIM1-deficient mice were previously described but showed only minor phenotypic aberrations. To assess the role of PIM proteins in mammalian physiology, compound Pim knockout mice were generated. Mice lacking expression of Pim1, Pim2, and Pim3 are viable and fertile. However, PIM-delficient mice show a profound reduction in body size at birth and throughout postnatal life. In addition, the in vitro response of distinct hematopoietic cell populations to growth factors is severely impaired. In particular, PIM proteins are required for the efficient proliferation of peripheral T lymphocytes mediated by synergistic T-cell receptor and interleukin-2 signaling. These results indicate that members of the PIM family of proteins are important but dispensable factors for growth factor signaling.

Original languageEnglish
Pages (from-to)6104-6115
Number of pages12
JournalMolecular and Cellular Biology
Volume24
Issue number13
DOIs
Publication statusPublished - Jul-2004
Externally publishedYes

Keywords

  • CELL-CYCLE PROGRESSION
  • E-MU-MYC
  • PROTEIN-KINASE
  • C-MYC
  • INHIBITS APOPTOSIS
  • GENE-EXPRESSION
  • MUTANT MICE
  • BONE-MARROW
  • T-CELLS
  • PROLIFERATION

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