| Abstract: |
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. Copyright © 2009, American Society for Microbiology. All Rights Reserved. |
| Keywords: |
signal transduction; controlled study; protein expression; genetics; nonhuman; t lymphocyte; t-lymphocytes; mouse; animal; cytology; metabolism; mammalia; animals; mice; animal tissue; gene targeting; gene expression; spleen; germ cell; animal experiment; transcription factor; cell fate; in vivo study; bacteria (microorganisms); mice, inbred c57bl; b lymphocyte induced maturation protein 1; red fluorescent protein; photoprotein; prdm1 protein, mouse; virus receptor; avian leukosis oncovirus; avian leukosis oncovirus b; b lymphocyte; bacterial artificial chromosome; bird disease; carcinogenesis; cell lineage; cell specificity; cell type; gene transfer; genetic manipulation; immunoregulation; leukemia virus; transgenic animal; transgenic mouse; viral gene delivery system; c57bl mouse; gene vector; genetic transduction; virology; animalia; avian leukosis virus; mus musculus; subgroup b; b-lymphocytes; chromosomes, artificial, bacterial; genetic vectors; luminescent proteins; mice, transgenic; receptors, virus; transcription factors; transduction, genetic
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