Analysis of Pim-1 function in mutant mice.
The Pim-1 gene has frequently been found activated by proviral insertion in haematopoietic tumors in mice. The fact that overexpression of Pim-1 can contribute to lymphomagenesis was formally proven by overexpressing a Pim-1 transgene in lymphoid cells. The transgene induces a low incidence of T cell lymphomas and an increased susceptibility to chemically (ENU) and virally (MoMuLV) induced lymphomas. The mouse Pim-1 gene encodes two cytoplasmic protein-serine/threonine kinases. Northern analysis shows the highest expression to be in haematopoietic tissues, especially early in development. High expression has also been noted in testis and ES cells. Expression can be induced by growth factors and mitogens. The gene is evolutionarily highly conserved. Inactivation of both Pim-1 alleles in ES cells or mice did not reveal any obvious abnormalities. In order to look more closely for possible haematopoietic abnormalities specific growth factor response were studied in vitro. The IL-3 response of bone marrow-derived mast-cell cultures (BMMC) was found to be severely impaired in mast cells derived from Pim-1 deficient mice.
Domen
J
J
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
van der Lugt
N M
NM
Laird
P W
PW
Saris
C J
CJ
Berns
A
A
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005838:Genotype; D007377:Interleukin-3 / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1; D011519:Proto-Oncogenes / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1