Disease relevance of SLC11A1

• Polymorphisms at the bovine Nramp1 3' untranslated region (3'UTR), detectable by Single Strand Conformational Analysis (SSCA), are associated with natural resistance against brucellosis [1].
• The natural resistance associated macrophage protein 1 (Nramp1) has been reported to confer resistance or susceptibility to Mycobacterium bovis, Salmonella typhimurium, and Leishmania donovani in the mouse, Mus musculus [2].
• By Western blotting, we demonstrate high-level expression of NRAMP1 proteins in peripheral blood cells and granulomas of Mycobacterium bovis-infected bovines [3].
• Stable transfection of the bovine NRAMP1 gene into murine RAW264.7 cells: effect on Brucella abortus survival [4].
• Coexpression of NRAMP1, iNOS, and Nitrotyrosine in Bovine Tuberculosis [5].

High impact information on SLC11A1

• Northern blotting indicated that bovine NRAMP1 was expressed primarily in macrophages and tissues of the recticuloendothelial system [6].
• Protective effect of the Nramp1 BB genotype against Brucella abortus in the water buffalo (Bubalus bubalis) [7].
• The monocytes from the BB (resistant) subjects displayed a higher basal level of Nramp1 mRNA and a lower number of viable intracellular bacteria than did the monocytes from AA (susceptible) subjects [7].
• High-level expression of NRAMP1 in peripheral blood cells and tuberculous granulomas from Mycobacterium bovis-infected bovines [3].
• We developed an in vitro model for expression of resistance- and susceptibility-associated alleles of bovine NRAMP1 as stable transgenes under the regulatory control of the bovine NRAMP1 promoter in the murine RAW264.7 macrophage cell line (Bcg(s)) to analyze the regulation of the NRAMP1 gene and its role in macrophage function [4].

Biological context of SLC11A1

• Nramp1 gene in mouse plays a critical role in innate immunity favoring bacterial killing by macrophages in addition to its influence on adaptative immunity [1].
• The association of NRAMP 1 gene polymorphisms with disease in cattle has been limited to a single microsatellite located within the 3'-non coding region of the bovine NRAMP 1 gene [8].
• Comparison of the bovine, murine and human NRAMP 1 gene structures revealed a high degree of conservation in intron placement, though the lengths of several introns were less-well conserved [8].
• All the breeds of cattle and buffaloes tested in this study coded for Gly at the position in exon VI which corresponds to the same amino acid of the murine Nramp1-resistant phenotype at position 169 [2].
• In order to facilitate further studies on this important gene, we now report the nearly complete structure of the bovine NRAMP 1 gene, including sizes and positions of 13 introns relative to the bovine NRAMP 1 gene coding sequence and the DNA sequence of intron-exon junctions [8].

Anatomical context of SLC11A1

• An NRAMP1-glutathione S-transferase fusion protein was used to test the ability of the NRAMP1 NH2-terminal domain to bind to taxol-stabilized microtubules [9].
• In this work we demonstrate by Western blot a high expression of NRAMP1 in peripheral blood mononuclear cells (PBMCs), alveolar macrophages (obtained by bronchioalveolar lavage), and lymph node granulomas from 8 Holstein-Freisian cattle with autopsy-proven bovine TB [5].
• This study shows that the expression of NRAMP1 and iNOS is costimulated in granulomas, which are protective T-cell reactions against mycobacteria [5].

Other interactions of SLC11A1

• Two new markers, NRAMP1 and ACTA1, were added to the linkage maps on BTA2 and BTA28, respectively [10].

Analytical, diagnostic and therapeutic context of SLC11A1

• Sequence analysis of the NRAMP1 genes from different bovine and buffalo breeds [2].
• We tested 231 water buffalo cows for the presence of anti-Brucella abortus antibodies (by the agglutination and complement fixation tests) and the Nramp1 genotype (by PCR-denaturing gradient gel electrophoresis) [11].
• Immunohistochemistry revealed the abundant expression of NRAMP1 and iNOS in lymph node and lung granulomas [5].

References