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Journal of Virology, May 2009, p. 4835-4843, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02254-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cell-Specific Transduction of Prdm1-Expressing Lineages Mediated by a Receptor for Avian Leukosis Virus Subgroup B{triangledown} ,{dagger}

Fotis Asimakopoulos1,2* and Harold E. Varmus1

Cancer Biology and Genetics Program,1 Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 100652

Received 27 October 2008/ Accepted 2 March 2009

The transcription factor Blimp-1 has emerged as a regulator of cell fate in embryonic (germ cell) and adult (B- and T-cell immune effector and epithelial) lineages. It has also been proposed to act as a tumor suppressor in B-cell malignancy. Here, we present a novel in vivo system enabling the targeted genetic manipulation of cells expressing Prdm1, the gene encoding Blimp-1. We created bacterial artificial chromosome-transgenic mice expressing the avian leukosis virus (ALV) receptor TVB, fused to monomeric red fluorescent protein, under regulation by Prdm1 transcriptional elements, and we achieved transduction of TVB-expressing lymphocytes by ALV vectors bearing a subgroup B envelope. The system presented here incorporates a number of innovations. First, it is the first mammalian transgenic system that employs the ALV receptor TVB, thus expanding the flexibility and scope of ALV-mediated gene delivery. Second, it represents the first ALV-based system that allows gene transfer and expression into in vivo-activated mature lymphocytes, a cell type that has traditionally presented formidable challenges to efficient retroviral transduction. Third, Prdm1:TVB-mRFP transgenic animals could provide an invaluable tool for exploring the diverse roles of Blimp-1 in lineage commitment, immune regulation, and tumorigenesis.

* Corresponding author. Mailing address: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065. Phone: (646) 888-3001. Fax: (646) 888-3010. E-mail: asimakof{at}mskcc.org

{triangledown} Published ahead of print on 11 March 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, May 2009, p. 4835-4843, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02254-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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