Nucleic Acids Research, 1993, Vol. 21, No. 20 4750-4755
© 1993
MOLECULAR BIOLOGY |
In vivo analysis of Pim-1 deficiency
Division of Molecular Genetics, The Netherlands Cancer Institute and Department of Biochemistry, University of Amsterdam Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands 1Cancer Research Campaign Laboratories, Department of Pathology Edinburgh, UK 2AFRC Centre for Genome Research, University of Edinburgh Edinburgh, UK
*To whom correspondence should be addressed at present address: The Whitehead Institute for Biomedical Research, Room 455, Nine Cambridge Center, Cambridge MA 02142, USA
Received July 7, 1993. Revised August 23, 1993. Accepted August 23, 1993.
The Pim-1 proto-oncogene encodes a highly conserved serine/threonine phosphokinase (1–5) which is predominantly expressed in hematopoietic organs and gonads in mammals (6-9). Overexpression of Pim-1 predisposes to lymphomagenesis in mice (8, 10, 11). To develop a further understanding of Pim-1 in molecular terms, as well as in terms of its potential role in hematopoietic development, we have generated mice deficient in Pim-1 function. P/m-7-deficient mice are ostensibly normal, healthy and fertile. Detailed comparative analyses of the hematopoietic systems of the mutant mice and their wild-type littermates showed that they are indistinguishable for most of the parameters studied. Our analyses revealed one unexpected phenotype that correlated with the level of Pim-1 expression: Pim-1 deficiency correlated with a erythrocyte microcytosis, whereas overexpression of Pim-1 in E/i-P/7n-7-transgenic mice resulted in erythrocyte macrocytosis. In order to confirm that the observed decrease in erythrocyte Mean Cell Volume (MCV) was attributable to the Pim-1 deficiency, we developed mice transgenic for a Pim-1 gene construct with its own promoter and showed that this transgene could restore the low erythrocyte Mean Cell Volume observed in the Pirn-/-deficient mice to near wild-type levels. These results might be relevant to the observed involvement of the Pim-1 gene in mouse erythroleukemogenesis (12). The surprising lack of a readily observed phenotype in the lymphoid compartment of the P/m-7-deficient mice, suggests a heretofore unrecognized degree of in vivo functional redundancy of this highly conserved proto-oncogene.
+Present address: Institute of Cell and Molecular Biology, Darwin Building, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, UK
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