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Journal of Virology, February 2002, p. 1991-1994, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1991-1994.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Frequency of Missense Mutations in the Coding Region of a Eukaryotic Gene Transferred by Retroviral Vectors

Maria De Angioletti,^1, Ana Rovira,^1, Michel Sadelain,¹ Lucio Luzzatto,^1,2* and Rosario Notaro^1,2

Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 ,¹ IST—Istituto Nazionale per la Ricerca sul Cancro, 16132 Genoa, Italy²

Received 1 August 2001/ Accepted 19 October 2001

A relatively high mutation rate is probably a major factor in the evolutionary success of retroviruses, because it generates the genetic diversity that helps them to cope with changes in the environment. When using recombinant retroviruses as vectors for gene transfer and gene therapy, it is important to consider the implications of this biological characteristic. Until now, the mutation rate has been studied by using noneukaryotic genes as reporters. Here we report point mutations in the human glucose-6-phosphate dehydrogenase (hG6PD) gene transferred by Moloney murine leukemia virus-based vectors into murine bone marrow cells and NIH 3T3 murine fibroblasts. After bone marrow transplantation, we observed an hG6PD with abnormal electrophoretic mobility for 2 out of 34 mice. Next, we studied this phenomenon quantitatively and found 1 electrophoretically abnormal hG6PD variant among 93 independently isolated NIH 3T3 clones, from which we estimate a mutation rate of 1.4 x 10^-5 per base pair per replication cycle. Mutations in the transferred gene can thus contribute to the impairment of the effectiveness of retrovirus-mediated gene transfer.

Present address: IIGB-CNR, 80125 Naples, Italy.

Present address: Institut de Biotecnologia i de Biomedicina "Vincent Villar I Palasí," Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

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