Transcriptional activity of the CD45 gene promoter in retroviral vector constructs.
Both specific and housekeeping transcriptional control elements have been successfully used to generate retroviral vectors that express in a stable tissue specific manner. However, no such vectors have been developed specifically for expression in haematopoietic cells. This paper describes the construction of retroviral vectors incorporating sequences from the promoter region of the murine CD45 (leucocyte common antigen) gene and using the human alpha-L-iduronidase cDNA as a reporter gene. These vectors were tested for expression of the alpha-L-iduronidase gene in skin fibroblasts and a lymphoblastoid cell line which is permissive for CD45 expression, derived from patients with mucopolysaccharidosis type I (MPS I, alpha-L-iduronidase deficiency). The results obtained demonstrate that, in the context of a retroviral construct, the activity of the CD45 gene promoter in lymphocytes and fibroblasts parallels the activity of the retroviral long terminal repeat (LTR). These results suggest that additional transcriptional control elements from the CD45 gene, or other haematopoietic specific genes, will be necessary for the construction of a haematopoietic specific vector.
Anson
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DS
Department of Chemical Pathology, Adelaide Childrens Hospital, SA, Australia.
Occhiodoro
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D000818:Animals; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D007068:Iduronidase / Q000096:biosynthesis / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000235:genetics*; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D051379:Mice; D008059:Mucopolysaccharidosis I / Q000201:enzymology / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012190:Retroviridae / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
D011993:Recombinant Fusion Proteins; D017493:Leukocyte Common Antigens; D007068:Iduronidase