The Bcg/Ity/Lsh locus: genetic transfer of resistance to infections in C57BL/6J mice transgenic for the Nramp1 Gly169 allele
Open accessAbstract
The murine Bcg/Ity/Lsh locus determines the susceptibilities of inbred strains to infection with unrelated intracellular parasites, such as Mycobacterium bovis, Salmonella typhimurium, and Leishmania donovani. A candidate for Bcg/Ity/Lsh, designated Nramp1, has been recently identified and shown to encode a novel integral membrane protein that is expressed exclusively in professional phagocytes but whose function remains unknown. In inbred strains, the susceptibility to infection is associated with a single glycine-to-aspartic acid substitution at position 169 (G169D) in the predicted TM4 of the protein. To confirm the candidacy of Nramp1 as Bcg/Ity/Lsh and to determine the importance of the G169D mutation on Nramp1 function, we constructed transgenic mice in which the G169 allele of Nramp1 was transferred onto the background of a homozygous D169 allele. These transgenic mice were analyzed for their sensitivity to infections under the control of Bcg/Ity/Lsh. The transgene constructed for these studies contained the entire Nramp1G169 gene together with approximately 5 kb of sequences upstream of the transcription initiation site of this gene. We observed that these sequences were sufficient to direct Nramp1G169 expression in transgenic macrophages, resulting in the appearance of a mature protein of 90 to 100 kDa over a background of Nramp1G169 characterized by the complete absence of the mature Nramp1 polypeptide. The appearance of the Nramp1G169-encoded protein in transgenic macrophages was concomitant with the emergence of resistance to infection by M. bovis BCG, as measured by the extent of bacteria] replication in the spleen, and by S. typhimurium, as measured by survival after an intravenous challenge. The gain of function detected in transgenic Nramp1G169 animals establishes unambiguously that Nramp1 and Bcg/Ity/Lsh are allelic.
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Slc11a1 coding rather than regulatory region variation is relevant to a broader spectrum of intracellular infectious agents including Francisella tularensis and S. Typhimurium.
“coding rather than in the regulatory region of Slc11a1, which is relevant to a broader spectrum of intracellular infectious agents also including Francisella tularensis and S. Typhimurium (Govoni et al., 1996;Kovarova et al., 2000;Vidal et al., 1995).”
From Iron in infection and immunity (2020) · cites this paper as Govoni et al., 1996
Cites
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
Feinberg, A. P., & Vogelstein, B. (1983) · Analytical Biochemistry · doi:10.1016/0003-2697(83)90418-9 · Cited by 24,512 · see citing works
Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive
Denning, G. M., Anderson, M. P., Amara, J. F., Marshall, J., Smith, A. E., & Welsh, M. J. (1992) · Nature · doi:10.1038/358761a0 · Cited by 1,236 · see citing works
Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg
Vidal, S. M., Malo, D., Vogan, K., Skamene, E., & Gros, P. (1993) · Cell · doi:10.1016/0092-8674(93)90135-d · Cited by 1,104 · see citing works
Self-citationVidal, S., Tremblay, M. L., Govoni, G., Gauthier, S., Sebastiani, G., Malo, D., Skamene, E., Olivier, M., Jothy, S., & Gros, P. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.3.655 · Cited by 603 · see citing works
Self-citationGenetic regulation of resistance to intracellular pathogens
Skamene, E., Gros, P., Forget, A., Kongshavn, P. A. L., Charles, C. S., & Taylor, B. A. (1982) · Nature · doi:10.1038/297506a0 · Cited by 372 · see citing works
Self-citationNramp defines a family of membrane proteins.
Cellier, M. F., Privé, G. G., Belouchi, A., Kwan, T., Rodrigues, V., Chia, W., & Gros, P. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.22.10089 · Cited by 349 · see citing works
Self-citationGenetic control of natural resistance to Mycobacterium bovis (BCG) in mice.
Gros, P., Skamene, E., & Forget, A. (1981) · The Journal of Immunology · doi:10.4049/jimmunol.127.6.2417 · Cited by 343 · see citing works
Self-citationGenetics of Resistance to Infection with Salmonella typhimurium in Mice
Plant, J. E., & Glynn, A. A. (1976) · The Journal of Infectious Diseases · doi:10.1093/infdis/133.1.72 · Cited by 320 · see citing works
Malo, D., Vogan, K. J., Vidal, S. M., Hu, J., Cellier, M. F., Schurr, E., Fuks, A., Bumstead, N., Morgan, K. W., & Gros, P. (1994) · Genomics · doi:10.1006/geno.1994.1458 · Cited by 259 · see citing works
Self-citationLissner, C. R., Swanson, R. N., & O’Brien, A. D. (1983) · The Journal of Immunology · doi:10.4049/jimmunol.131.6.3006 · Cited by 246 · see citing works
Vidal, S. M., Pinner, E., Lepage, P., Gauthier, S., & Gros, P. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.8.3559 · Cited by 241 · see citing works
Self-citationDj, B. (1977) · PubMed · Cited by 225 · see citing works
Denning, G. M., Ostedgaard, L. S., & Welsh, M. J. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.118.3.551 · Cited by 171 · see citing works
The interleukin-8-receptor family: from chemokines to malaria
Horuk, R. (1994) · Immunology Today · doi:10.1016/0167-5699(94)90314-x · Cited by 169 · see citing works
Resistance of Inbred Mice to Salmonella typhimurium
Robson, H. G., & Vas, S. I. (1972) · The Journal of Infectious Diseases · doi:10.1093/infdis/126.4.378 · Cited by 160 · see citing works
Expression of the natural resistance gene Lsh in resident liver macrophages
Crocker, P. R., Blackwell, J. M., & Bradley, D. J. (1984) · Infection and Immunity · doi:10.1128/iai.43.3.1033-1040.1984 · Cited by 140 · see citing works
Functional consequences of glycine mutations in the predicted cytoplasmic loops of P-glycoprotein.
Loo, T. W., & Clarke, D. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37274-5 · Cited by 128 · see citing works
Loo, T. W., & Clarke, D. M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.37.21839 · Cited by 124 · see citing works
Phenotypic expression of genetically-controlled natural resistance to Mycobacterium bovis (BCG).
Jl, S., Gros, P., Forget, A., & Skamene, E. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.132.2.888 · Cited by 122 · see citing works
Self-citationCellular mechanisms of genetically controlled host resistance to Mycobacterium bovis (BCG).
Gros, P., Skamene, E., & Forget, A. (1983) · The Journal of Immunology · doi:10.4049/jimmunol.131.4.1966 · Cited by 111 · see citing works
Self-citationGovoni, G. R., Vidal, S. M., Cellier, M. F., Lepage, P., Malo, D., & Gros, P. (1995) · Genomics · doi:10.1006/geno.1995.1002 · Cited by 104 · see citing works
Self-citationSchurr, E., Raymond, M., Bell, J. C., et al. (1989) · PubMed · Cited by 97 · see citing works
Regulation of resistance to leprosy by chromosome 1 locus in the mouse
Skamene, E., Gros, P., Forget, A., Patel, P. J., & Nesbitt, M. N. (1984) · Immunogenetics · doi:10.1007/bf00387854 · Cited by 93 · see citing works
Self-citationBarton, C. H., White, J. K., Roach, T. I. A., & Blackwell, J. M. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.5.1683 · Cited by 92 · see citing works
Cellier, M. F., Shustik, C., Dalton, W. S., Rich, E. A., Hu, J., Malo, D., Schurr, E., & Gros, P. (1997) · Journal of Leukocyte Biology · doi:10.1002/jlb.61.1.96 · Cited by 81 · see citing works
Self-citationBenjamin, W. H., Hall, P., Roberts, S., & Briles, D. E. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.144.8.3143 · Cited by 76 · see citing works
Regulation of host resistance toMycobacterium intracellulare in vivo and in vitro by theBcg gene
Goto, Y., Buschman, E., & Skamene, E. (1989) · Immunogenetics · doi:10.1007/bf02421210 · Cited by 65 · see citing works
Self-citationHigh-Resolution Linkage Map in the Vicinity of the Host Resistance Locus Bcg
Malo, D., Vidal, S. M., Hu, J., Skamene, E., & Gros, P. (1993) · Genomics · doi:10.1006/geno.1993.1244 · Cited by 63 · see citing works
Self-citationA ‘safe-site’ for Salmonella typhimurium is within splenic polymorphonuclear cells
Dunlap, N. E., Benjamin, W. H., Berry, A., et al. (1992) · Microbial Pathogenesis · doi:10.1016/0882-4010(92)90019-k · Cited by 57 · see citing works
Cerretti, D. P., Nelson, N., Kozlosky, C. J., Morrissey, P., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Dosik, J. K., & Mock, B. A. (1993) · Genomics · doi:10.1006/geno.1993.1486 · Cited by 57 · see citing works
White, J. K., Shaw, M., Barton, C. H., Cerretti, D. P., Williams, H. P., Mock, B. A., Carter, N. P., Peacock, C. S., & Blackwell, J. M. (1994) · Genomics · doi:10.1006/geno.1994.1619 · Cited by 55 · see citing works
Kniep, E., Domzig, W., Lohmann-Matthes, M. L., & Kickhöfen, B. (1981) · The Journal of Immunology · doi:10.4049/jimmunol.127.2.417 · Cited by 53 · see citing works
Killing of Mycobacterium smegmatis by Macrophages From Genetically Susceptible and Resistant Mice
Denis, M., Forget, A., Pelletier, M., Gervais, F., & Skamene, E. (1990) · Journal of Leukocyte Biology · doi:10.1002/jlb.47.1.25 · Cited by 45 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Gruenheid, S., Pinner, E., Desjardins, M., & Gros, P. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.4.717 · Cited by 428 · see citing works
Self-citationDivalent-metal transport by NRAMP proteins at the interface of host–pathogen interactions
Forbes, J. R., & Gros, P. (2001) · Trends in Microbiology · doi:10.1016/s0966-842x(01)02098-4 · Cited by 424 · see citing works
Self-citationIron in infection and immunity
Nairz, M., & Weiss, G. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100864 · Cited by 359 · see citing works
Iron-withholding strategy in innate immunity
Ong, S. T., Shan Ho, J. Z., Ho, B., & Ding, J. L. (2006) · Immunobiology · doi:10.1016/j.imbio.2006.02.004 · Cited by 269 · see citing works
Hackam, D. J., Rotstein, O. D., Zhang, W.-J., Gruenheid, S., Gros, P., & Grinstein, S. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.2.351 · Cited by 202 · see citing works
Self-citationRole of Iron in<i>Nramp1</i>-Mediated Inhibition of Mycobacterial Growth
Zwilling, B. S., Kuhn, D. E., Wikoff, L., Brown, D., & Lafuse, W. (1999) · Infection and Immunity · doi:10.1128/iai.67.3.1386-1392.1999 · Cited by 155 · see citing works
Understanding the multiple functions of Nramp1
Blackwell, J. M., Searle, S., Goswami, T., & Miller, E. N. (2000) · Microbes and Infection · doi:10.1016/s1286-4579(00)00295-1 · Cited by 136 · see citing works
Karlinsey, J. E., Maguire, M. E., Becker, L. A., Crouch, M. V., & Fang, F. C. (2010) · Molecular Microbiology · doi:10.1111/j.1365-2958.2010.07357.x · Cited by 102 · see citing works
The natural resistance-associated macrophage protein and susceptibility to intracellular pathogens
Bellamy, R. (1999) · Microbes and Infection · doi:10.1016/s1286-4579(99)80010-0 · Cited by 96 · see citing works
Zaharik, M. L., Vallance, B. A., Puente, J. L., Gros, P., & Finlay, B. B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252415599 · Cited by 96 · see citing works
Self-citationBarton, C. H., Biggs, T. E., Baker, S. T., Bowen, H., & Atkinson, P. G. P. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.66.5.757 · Cited by 88 · see citing works
Nramp1 locus encodes a 65 kDa interferon-γ-inducible protein in murine macrophages
ATKINSON, P. G. P., BLACKWELL, J. M., & BARTON, C. H. (1997) · Biochemical Journal · doi:10.1042/bj3250779 · Cited by 81 · see citing works
Consequence of <i>Nramp1</i> Deletion to <i>Mycobacterium tuberculosis</i> Infection in Mice
North, R. J., LaCourse, R., Ryan, L., & Gros, P. (1999) · Infection and Immunity · doi:10.1128/iai.67.11.5811-5814.1999 · Cited by 76 · see citing works
Self-citationLang, T., Prina, E., Sibthorpe, D., & Blackwell, J. M. (1997) · Infection and Immunity · doi:10.1128/iai.65.2.380-386.1997 · Cited by 75 · see citing works
Riedelberger, M., Penninger, P., Tscherner, M., Seifert, M., Jenull, S., Brunnhofer, C., Scheidl, B., Tsymala, I., Bourgeois, C., Petryshyn, A., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.01.023 · Cited by 64 · see citing works
Brown, D. E., Libby, S. J., Moreland, S. M., McCoy, M. W., Brabb, T., Stepanek, A., Fang, F. C., & Detweiler, C. S. (2013) · Veterinary Pathology · doi:10.1177/0300985813478213 · Cited by 48 · see citing works
Loomis, W. P., Johnson, M. L., Brasfield, A., Blanc, M.-P., Yi, J., Miller, S. I., Cookson, B. T., & Hajjar, A. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111763 · Cited by 36 · see citing works
“Oligo dT primed cDNA was reverse transcribed using Superscript II Reverse Transcriptase (Invitrogen, Carlsbad, CA), and MinusRT controls were run for each sample.”
InfluentialSalmonella enterica Infection Stimulates Macrophages to Hemophagocytose
Pilonieta, M. C., Moreland, S. M., English, C. N., & Detweiler, C. S. (2014) · mBio · doi:10.1128/mbio.02211-14 · Cited by 35 · see citing works
Kovářová, H., Hernychová, L., Hajdúch, M., Šírová, M., & Macela, A. (2000) · Infection and Immunity · doi:10.1128/iai.68.3.1480-1484.2000 · Cited by 17 · see citing works
- Authors
- Govoni, G., Vidal, S., Gauthier, S., Skamene, E., Malo, D., & Gros, P.
- Affiliations
- McGill University (CA)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 1996-08
- Volume
- 64
- Issue
- 8
- Pages
- 2923-2929
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC174168
- OpenAlex
- W2113997284
- Cited by
- 167
- References
- 33
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 2 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 7 · 2013: 2 · 2012: 5
- FWCI
- 13.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI035237, 1RO1AI35237-01)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- NRAMP1, transgenic mice, Mycobacterium bovis BCG, Salmonella typhimurium, Leishmania donovani, macrophages, professional phagocytes, gain-of-function
- MeSH terms
- Natural Resistance-associated Macrophage Protein 1, Alleles, Animals, Carrier Proteins, Chromosome Mapping, Crosses, Genetic, Female, Genotype, Glycine, Immunity, Innate, Male, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Mycobacterium bovis, Tuberculosis, Cation Transport Proteins, Mice
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