In vivo analysis of Pim-1 deficiency.
The Pim-1 proto-oncogene encodes a highly conserved serine/threonine phosphokinase which is predominantly expressed in hematopoietic organs and gonads in mammals. Overexpression of Pim-1 predisposes to lymphomagenesis in mice. 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. Pim-1-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 mu-Pim-1-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 Pim-1-deficient mice to near wild-type levels. These results might be relevant to the observed involvement of the Pim-1 gene in mouse erythroleukemogenesis. The surprising lack of a readily observed phenotype in the lymphoid compartment of the Pim-1-deficient mice, suggests a heretofore unrecognized degree of in vivo functional redundancy of this highly conserved proto-oncogene.
Laird
P W
PW
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
van der Lugt
N M
NM
Clarke
A
A
Domen
J
J
Linders
K
K
McWhir
J
J
Berns
A
A
Hooper
M
M
D000818:Animals; D005260:Female; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009857:Oncogenes; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D051573:Proto-Oncogene Proteins c-pim-1; D015183:Restriction Mapping
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1