Targeted disruption of the mouse ing1 locus results in reduced body size, hypersensitivity to radiation and elevated incidence of lymphomas.
Ing1 belongs to the family of evolutionary conserved genes encoding nuclear PHD finger-containing proteins implicated in a variety of processes, including tumorigenesis, replicative senescence, excision repair and response to genotoxic stress. We have generated mice deficient in all the isoforms of Ing1 by targeted disruption of the exon that is common for all ing1 transcripts. Embryonic fibroblasts from ing1-knockout mice were similar to the wild-type cells in their growth characteristics, replicative lifespan in culture, p53 induction and sensitivity to various cytotoxic treatments with minor alterations in cell cycle distribution in response to genotoxic stress. ing1-deficient animals are characterized by reduced size with no obvious morphological, physiological or behavioral abnormalities, indicating that ing1 function is dispensable for the viability of mice under normal physiological conditions. Loss of ing1 was associated with earlier onset and higher incidence of lymphomas. Consistent with the possible involvement of Ing1 in DNA repair, ing1-deficient mice were more sensitive to total body gamma radiation. Our observations are well in line with the suggested role of ing1 as a candidate tumor suppressor gene involved in control of DNA damage response.
Kichina
J V
JV
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Zeremski
M
M
Aris
L
L
Gurova
K V
KV
Walker
E
E
Franks
R
R
Nikitin
A Y
AY
Kiyokawa
H
H
Gudkov
A V
AV
D000015:Abnormalities, Multiple / Q000235:genetics; D017668:Age of Onset; D000375:Aging / Q000235:genetics; D000818:Animals; D049628:Body Size / Q000235:genetics*; D002478:Cells, Cultured; D004260:DNA Repair / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008223:Lymphoma / Q000453:epidemiology* / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays; D014916:Whole-Body Irradiation
C501505:Ing1 protein, mouse; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins