Modular usage of the HLA-DRA promoter in extra-hematopoietic and hematopoietic cell types of transgenic mice.
Class II MHC genes (for example, the human HLA-DRA gene) are expressed at the cell surface in many professional and nonprofessional antigen-presenting cells in a variety of anatomical locations. Here, we report about 13 mouse transgenic lines (11 of which have not been previously described) generated with four distinct sets of DRA transgenes carrying progressive, informative 5' and 3' deletions. DRA expression was assessed in B lymphocytes, dendritic cells, macrophages, and extra-hematopoietic cells (particularly kidney epithelial cells). A compact transcriptional unit was identified that efficiently directs DRA expression [both constitutive and interferon (IFN)-gamma induced] in extra-hematopoietic tissues and dendritic cells. It extends from position -266 upstream of the transcription initiation site to position +119 downstream of the last DRA exon. The same fragment, however, did not efficiently direct IFN-gamma-induced DRA expression in macrophages, that required additional 5' sequences. Thus, IFN-gamma uses distinct promoter segments and mechanisms to up-regulate class II in different cell lineages. In contrast to previous results in transgenic mice expressing murine class II transgenes, we were unable to generate reproducible patterns of HLA-DRA expression in B cells.
Giorda
Ezio
E
Laboratory of Immunology, Regina Elena Cancer Institute CRS, Rome, Italy.
Sibilio
Leonardo
L
Martayan
Aline
A
Feriotto
Giordana
G
Bianchi
Nicoletta
N
Mischiati
Carlo
C
Di Rosa
Francesca
F
Pozzi
Laura
L
Gambari
Roberto
R
Giacomini
Patrizio
P
D024509:3' Flanking Region; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002460:Cell Line; D003713:Dendritic Cells / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000235:genetics* / Q000378:metabolism; D059805:HLA-DR alpha-Chains; D006413:Hematopoietic System / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics
D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D007371:Interferon-gamma