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Molecular and Cellular Biology, July 2004, p. 6104-6115, Vol. 24, No. 13
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.13.6104-6115.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mice Deficient for All PIM Kinases Display Reduced Body Size and Impaired Responses to Hematopoietic Growth Factors{dagger}

Harald Mikkers,1,{ddagger} Martijn Nawijn,1 John Allen,1,§ Conny Brouwers,2 Els Verhoeven,1 Jos Jonkers,2 and Anton Berns1*

Division of Molecular Genetics and Centre of Biomedical Genetics,1 Division of Molecular Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands2

Received 20 November 2003/ Returned for modification 15 January 2004/ Accepted 29 February 2004

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-deficient 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.

* Corresponding author. Mailing address: Division of Molecular Genetics and Centre of Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Phone: 31 20 5121990. Fax: 31 20 5122011. E-mail: a.berns{at}nki.nl.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org.

{ddagger} Present address: Cell and Molecular Biology Department, Karolinska Institutet, S-171 77, Stockholm, Sweden.

§ Present address: Cancer Drug Resistance Group, Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW 2042, Australia.

Molecular and Cellular Biology, July 2004, p. 6104-6115, Vol. 24, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.13.6104-6115.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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