title: Functional analysis of 3'UTR polymorphisms in the caprine SLC11A1 gene and its association with the Mycobacterium avium subsp. paratuberculosis infection.
abstract: The study aimed to investigate whether the genetic polymorphisms in the 3'UTR of the caprine SLC11A1 gene are functional, and to assess the role of MAP as a regulatory parameter in gene expression. To this goal we constructed plasmids expressing the Luciferase reporter gene in transient transfections of a mouse (Balb/c) macrophage cell line (RAW264.7), incorporating those polymorphisms that our previous work indicated as more prominent in terms of SLC11A1 expression and responsiveness to MAP infection. Gene expression variation was recorded on the average of the respective measurements after exposure to Mycobacterium avium subsp. paratuberculosis (MAP) combined with microbial antigens and cytokines. In silico analysis of the region under study allowed identification of one cis-acting RNA element, five putative transcriptional regulatory elements and 85 3'end microRNA binding sites. The two polymorphic regions (regions A and B) of the 3'UTR of the caprine SLC11A1 gene were recognized as regulators of its activity, at transcriptional and post-transcriptional level. The GT16 polymorphism at region A, combined with the GT8 polymorphism at region B, results in up-regulation of the SLC11A1 gene. The specific genotype was also found to be more responsive to MAP exposure at a statistically significant level.
authors.affiliation: Department of Anatomy and Physiology of Farm Animals, Faculty of Animal Science and Aquaculture, Agricultural University of Athens, 75 Iera Odos st., 11855 Athens, Greece. Electronic address: takastella@hotmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Taka
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, 176 Michalakopoulou st., 11527 Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Gazouli
authors.affiliation: Department of Science, Agricultural University of Athens, 75 Iera Odos st., 11855 Athens, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Sotirakoglou
authors.affiliation: Department of Anatomy and Physiology of Farm Animals, Faculty of Animal Science and Aquaculture, Agricultural University of Athens, 75 Iera Odos st., 11855 Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Liandris
authors.affiliation: Department of Anatomy and Physiology of Farm Animals, Faculty of Animal Science and Aquaculture, Agricultural University of Athens, 75 Iera Odos st., 11855 Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Andreadou
authors.affiliation: Department of Anatomy and Physiology of Farm Animals, Faculty of Animal Science and Aquaculture, Agricultural University of Athens, 75 Iera Odos st., 11855 Athens, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Triantaphyllopoulos
authors.affiliation: Department of Anatomy and Physiology of Farm Animals, Faculty of Animal Science and Aquaculture, Agricultural University of Athens, 75 Iera Odos st., 11855 Athens, Greece.
authors.forename: J
authors.initials: J
authors.lastname: Ikonomopoulos
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D015511:Goat Diseases / Q000235:genetics / Q000276:immunology; D006041:Goats / Q000235:genetics* / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology / Q000472:pathogenicity*; D010283:Paratuberculosis / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic; D000067996:RAW 264.7 Cells; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D020413:3' Untranslated Regions; D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1
keywords: Infection; MAP; Polymorphisms; SLC11A1