1. ¹Department of Molecular Genetics, Lerner Research Institute, Cleveland, OH, USA
2. ²Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA
3. ³Cleveland BioLabs, Inc., Cleveland, OH, USA
4. ⁴Department of Quantitative Health Sciences, The Cleveland Clinic Foundation, Cleveland, OH, USA
5. ⁵Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA

Correspondence: Dr AV Gudkov, Department of Molecular Genetics, NC20, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. E-mail: gudkov@ccf.org

⁶These authors contributed equally to this work.

⁷Current address: Center for the Study of Hepatitis C, Weill Medical College of Cornell University, 525 E.68th Street, New York, NY 10021, USA.

Received 19 May 2005; Revised 28 July 2005; Accepted 4 August 2005; Published online 19 September 2005.

Abstract

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.