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ABSTRACT In inbred mouse strains, permissiveness to intracellular replication of _Legionella pneumophila_ is controlled by a single locus (_Lgn1_), which maps to a region within distal
Chromosome 13 that contains multiple copies of the gene baculoviral IAP repeat–containing 1 (_Birc1_, also called _Naip_; refs. 1–3). Genomic BAC clones from the critical interval were
transferred into transgenic mice to functionally complement the _Lgn1_-associated susceptibility of A/J mice to _L. pneumophila_. Here we report that two independent BAC clones that rescue
susceptibility have an overlapping region of 56 kb in which the entire _Lgn1_ transcript must lie. The only known full-length transcript coded in this region is _Birc1e_ (also called
_Naip5_). Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to
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support SIMILAR CONTENT BEING VIEWED BY OTHERS TNSEQ IDENTIFIES GENETIC REQUIREMENTS OF _MYCOBACTERIUM TUBERCULOSIS_ FOR SURVIVAL UNDER VACCINE-INDUCED IMMUNITY Article Open access 22 May
2025 POPULATION ANALYSIS OF _LEGIONELLA PNEUMOPHILA_ REVEALS A BASIS FOR RESISTANCE TO COMPLEMENT-MEDIATED KILLING Article Open access 09 December 2021 A MULTIPLEX CRISPR INTERFERENCE TOOL
FOR VIRULENCE GENE INTERROGATION IN _LEGIONELLA PNEUMOPHILA_ Article Open access 04 February 2021 ACCESSION CODES ACCESSIONS GENBANK/EMBL/DDBJ * AF131205 * AF242431 * NM_010870 REFERENCES *
Yoshida, S., Goto, Y., Mizuguchi, Y., Nomoto, K. & Skamene, E. Genetic control of natural resistance in mouse macrophages regulating intracellular _Legionella pneumophila_ multiplication
_in vitro_. _Infect. Immun._ 59, 428–432 (1991). CAS PubMed PubMed Central Google Scholar * Diez, E. et al. Genetic and physical mapping of the mouse host resistance locus _Lgn1_.
_Mamm. Genome_ 8, 682–685 (1997). Article CAS Google Scholar * Growney, J.D. & Dietrich, W.F. High-resolution genetic and physical map of the _Lgn1_ interval in C57BL/6J implicates
_Naip2_ or _Naip5_ in _Legionella pneumophila_ pathogenesis. _Genome Res._ 10, 1158–1171 (2000). Article CAS Google Scholar * McDade, J.E. et al. Legionnaires' disease: isolation of
a bacterium and demonstration of its role in other respiratory disease. _N. Engl. J. Med._ 297, 1197–1203 (1977). Article CAS Google Scholar * Horwitz, M.A. & Silverstein, S.C.
Legionnaires' disease bacterium (_Legionella pneumophila_) multiples intracellularly in human monocytes. _J. Clin. Invest._ 66, 441–450 (1980). Article CAS Google Scholar * Swanson,
M.S. & Isberg, R.R. Association of _Legionella pneumophila_ with the macrophage endoplasmic reticulum. _Infect. Immun._ 63, 3609–3620 (1995). CAS PubMed PubMed Central Google Scholar
* Yamamoto, Y., Klein, T.W., Newton, C.A. & Friedman, H. Interaction of _Legionella pneumophila_ with peritoneal macrophages from various mouse strains. _Adv. Exp. Med. Biol._ 239,
89–98 (1988). Article CAS Google Scholar * Yamamoto, Y., Klein, T.W., Newton, C.A., Widen, R. & Friedman, H. Growth of _Legionella pneumophila_ in thioglycolate-elicited peritoneal
macrophages from A/J mice. _Infect. Immun._ 56, 370–375 (1988). CAS PubMed PubMed Central Google Scholar * Beckers, M.C., Yoshida, S., Morgan, K., Skamene, E. & Gros, P. Natural
resistance to infection with _Legionella pneumophila_: chromosomal localization of the _Lgn1_ susceptibility gene. _Mamm. Genome_ 6, 540–545 (1995). Article CAS Google Scholar * Scharf,
J.M. et al. The mouse region syntenic for human spinal muscular atrophy lies within the _Lgn1_ critical interval and contains multiple copies of _Naip_ exon 5. _Genomics_ 38, 405–417 (1996).
Article CAS Google Scholar * Endrizzi, M.G., Hadinoto, V., Growney, J.D., Miller, W. & Dietrich, W.F. Genomic sequence analysis of the mouse _Naip_ gene array. _Genome Res._ 10,
1095–1102 (2000). Article CAS Google Scholar * Diez, E., Yaraghi, Z., MacKenzie, A. & Gros, P. The neuronal apoptosis inhibitory protein (Naip) is expressed in macrophages and is
modulated after phagocytosis and during intracellular infection with _Legionella pneumophila_. _J. Immunol._ 164, 1470–1477 (2000). Article CAS Google Scholar * Growney, J.D., Scharf,
J.M., Kunkel, L.M. & Dietrich, W.F. Evolutionary divergence of the mouse and human _Lgn1_/SMA repeat structures. _Genomics_ 64, 62–81 (2000). Article CAS Google Scholar * Holcik, M.
et al. The hippocampal neurons of neuronal apoptosis inhibitory protein 1 (NAIP1)-deleted mice display increased vulnerability to kainic acid- induced injury. _Proc. Natl. Acad. Sci. USA_
97, 2286–2290 (2000). Article CAS Google Scholar * Wright, E.K. et al. _Naip5_ affects host susceptibility to the intracellular pathogen _Legionella pneumophila_. _Curr. Biol._ 13, in the
press (2003). * Roy, N. et al. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. _Cell_ 80, 167–178 (1995). Article CAS
Google Scholar * Somerville, M.J. et al. Clinical application of the molecular diagnosis of spinal muscular atrophy: deletions of neuronal apoptosis inhibitor protein and survival motor
neuron genes. _Am. J. Med. Genet._ 69, 159–165 (1997). Article CAS Google Scholar * Haider, M.Z., Moosa, A., Dalal, H., Habib, Y. & Reynold, L. Gene deletion patterns in spinal
muscular atrophy patients with different clinical phenotypes. _J. Biomed. Sci._ 8, 191–196 (2001). Article CAS Google Scholar * Liston, P. et al. Suppression of apoptosis in mammalian
cells by _NAIP_ and a related family of IAP genes. _Nature_ 379, 349–353 (1996). Article CAS Google Scholar * Hozak, R.R., Manji, G.A. & Friesen, P.D. The BIR motifs mediate dominant
interference and oligomerization of inhibitor of apoptosis Op-IAP. _Mol. Cell. Biol._ 20, 1877–1885 (2000). Article CAS Google Scholar * Wu, G. et al. Structural basis of IAP recognition
by Smac/DIABLO. _Nature_ 408, 1008–1012 (2000). Article CAS Google Scholar * Koonin, E.V. & Aravind, L. The NACHT family—a new group of predicted NTPases implicated in apoptosis and
MHC transcription activation. _Trends Biochem. Sci._ 25, 223–224 (2000). Article CAS Google Scholar * Perrelet, D. et al. IAP family proteins delay motoneuron cell death _in vivo_. _Eur.
J. Neurosci._ 12, 2059–2067 (2000). Article CAS Google Scholar * Maier, J.K. et al. The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases 3 and 7. _J. Neurosci._ 22,
2035–2043 (2002). Article CAS Google Scholar * Gao, L.Y. & Abu Kwaik, Y. Apoptosis in macrophages and alveolar epithelial cells during early stages of infection by _Legionella
pneumophila_ and its role in cytopathogenicity. _Infect. Immun._ 67, 862–870 (1999). CAS PubMed PubMed Central Google Scholar * Muller, A., Hacker, J. & Brand, B.C. Evidence for
apoptosis of human macrophage-like HL-60 cells by _Legionella pneumophila_ infection. _Infect. Immun._ 64, 4900–4906 (1996). CAS PubMed PubMed Central Google Scholar * Watarai, M. et al.
_Legionella pneumophila_ is internalized by a macropinocytotic uptake pathway controlled by the Dot/Icm system and the mouse _Lgn1_ locus. _J. Exp. Med._ 194, 1081–1096 (2001). Article CAS
Google Scholar * Yaraghi, Z., Korneluk, R.G. & MacKenzie, A. Cloning and characterization of the multiple murine homologues of NAIP (neuronal apoptosis inhibitory protein). _Genomics_
51, 107–113 (1998). Article CAS Google Scholar * Endrizzi, M. et al. Comparative sequence analysis of the mouse and human _Lgn1_/SMA interval. _Genomics_ 60, 137–151 (1999). Article CAS
Google Scholar Download references ACKNOWLEDGEMENTS The authors thank A. MacKenzie and D. Malo for their help and support, N. Gendron and J. Penney for expert technical assistance,
members of the McGill Mouse Genetics Group for use of the BAC transgenic core and L. Simard and C.J. DiDonato for BAC clone 227n6. This work was supported by grants from the Network of
Centers of Excellence (Canadian Genetic Diseases Network) to P.G. P.G. is supported by a Distinguished Scientist award and E.D. by a studentship from the Canadian Institutes of Health
Research. The BAC transgenic core was supported by a grant from Innovation Quebec. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biochemistry, McGill University, 3655 Sir
William Osler Promenade, Montreal, H3G-1Y6, Quebec, Canada Eduardo Diez, Susan Gauthier, Michel Tremblay & Philippe Gros * Department of Biochemistry, Microbiology and Immunology,
University of Ottawa, Ottawa, Canada Seung-Hwan Lee & Silvia Vidal * Department of Pediatrics, University of Ottawa, Ottawa, Canada Zahra Yaraghi * McGill Cancer Center, McGill
University, Montreal, Canada Michel Tremblay & Philippe Gros Authors * Eduardo Diez View author publications You can also search for this author inPubMed Google Scholar * Seung-Hwan Lee
View author publications You can also search for this author inPubMed Google Scholar * Susan Gauthier View author publications You can also search for this author inPubMed Google Scholar *
Zahra Yaraghi View author publications You can also search for this author inPubMed Google Scholar * Michel Tremblay View author publications You can also search for this author inPubMed
Google Scholar * Silvia Vidal View author publications You can also search for this author inPubMed Google Scholar * Philippe Gros View author publications You can also search for this
author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Philippe Gros. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. RIGHTS AND
PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Diez, E., Lee, SH., Gauthier, S. _et al._ _Birc1e_ is the gene within the _Lgn1_ locus associated with resistance to
_Legionella pneumophila_. _Nat Genet_ 33, 55–60 (2003). https://doi.org/10.1038/ng1065 Download citation * Received: 19 September 2002 * Accepted: 06 November 2002 * Published: 16 December
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