Cell-specific transduction of Prdm1-expressing lineages mediated by a receptor for avian leukosis virus subgroup B.
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.
Asimakopoulos
Fotis
F
Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. asimakof@mskcc.org
Varmus
Harold E
HE
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D001402:B-Lymphocytes / Q000378:metabolism* / Q000821:virology; D022202:Chromosomes, Artificial, Bacterial; D005822:Genetic Vectors; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D014157:Transcription Factors / Q000235:genetics*; D014161:Transduction, Genetic; D000097573:Red Fluorescent Protein
D008164:Luminescent Proteins; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011991:Receptors, Virus; D014157:Transcription Factors; D000097573:Red Fluorescent Protein; C513258:Prdm1 protein, mouse