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Gene Review

Lcn2  -  lipocalin 2

Mus musculus

Synonyms: 24p3, AW212229, Lipocalin-2, NGAL, Neutrophil gelatinase-associated lipocalin, ...


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Disease relevance of Lcn2

  • However, we found that Lcn2-/- mice exhibited an increased susceptibility to bacterial infections, in keeping with the proposed function of lipocalin 2 in iron sequestration [1].
  • We analyzed Lcn2-/- mice using a mouse model for severe renal failure and could not detect any significant differences compared with their WT littermates [1].
  • Furthermore, we show that mice rapidly succumb to infection by an iroA-harboring strain of E. coli but not its wild-type counterpart, and that this increased virulence depends on evasion of host Lcn2 [2].
  • Here, we show that the iroA gene cluster, found in many pathogenic strains of Gram-negative enteric bacteria, including E. coli, Salmonella spp., and Klebsiella pneumoniae, allows bacteria to evade sequestration of Ent by Lcn2 [2].
  • Lcn2 is a member of the acute phase response family of proteins and its mRNA levels in the brain increase in response to inflammation [3].

High impact information on Lcn2

  • A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake [4].
  • 24p3 also induced apoptosis in a wide variety of leukocytes but not other cell types [5].
  • Neutrophils isolated from Lcn2-/- mice showed significantly less bacteriostatic activity compared with WT controls [1].
  • Analysis of Lcn2-/- mice showed normal cell death upon IL-3 withdrawal and normal kidney development [1].
  • We demonstrate that C-glucosylated derivatives of Ent produced by iroA-encoded enzymes do not bind purified Lcn2, and an iroA-harboring strain of E. coli is insensitive to the growth inhibitory effects of Lcn2 in vitro [2].

Chemical compound and disease context of Lcn2

  • In an established murine model of renal ischemia-reperfusion injury, intravenous NGAL administered before, during, or after ischemia resulted in marked amelioration of the morphologic and functional consequences, as evidenced by a significant decrease in the histopathologic damage to tubules and in serum creatinine measurements [6].
  • We recently demonstrated that enterochelin, a bacterial catecholate siderophore, binds to the host protein lipocalin 2 (ref. 5). Here, we show that this event is pivotal in the innate immune response to bacterial infection [7].

Biological context of Lcn2

  • The lipocalin 24p3 was reported to be secreted by mouse hematopoietic cells deprived of IL-3, resulting in apoptosis induction in a variety of hematopoietic cells including bone marrow cells [8].
  • These findings indicate that suppression of normal hematopoiesis in BCR-ABL-induced leukemia is an active process involving secretion of the cell death-inducing factor 24p3 by mouse leukemia cells, raising the possibility that similar factors are involved in BCR-ABL+ CML [8].
  • In this study, we assign the Lcn2 gene to rat chromosome band 3q12 by genetic linkage analysis [9].
  • In vitro studies have suggested that lipocalin 2 is important for cellular apoptosis induced by IL-3 withdrawal, and for the induction of kidney differentiation during embryogenesis [1].
  • These experiments demonstrate that the local expression of Ngal can play a regulatory role in epithelial morphogenesis by promoting the organization of cells into tubular structures while simultaneously negatively modulating the branching effects of HGF [10].

Anatomical context of Lcn2


Associations of Lcn2 with chemical compounds

  • The expression of the Bcr-Abl oncoprotein and its tyrosine kinase were required for induction of 24p3 expression [8].
  • Automated Edman degradation was unable to determine the N-terminal residue of the glycoprotein and the partial sequences determined from its trypsin digests were found to be identical with the protein sequence deduced from 24p3 cDNA [12].
  • Based on this observation, we examined the effect of a glucocorticoid (dexamethasone, Dex) on 24p3 expression [14].
  • We report here that spermatozoa, from the caudal epididymis, demonstrate the ability to bind with 24p3 protein and further internalize it and deliver the ferric ion to the spermatozoa via protein internalization [15].
  • Using a fluorometric method, the binding affinities of ferrous ion and ferric ion to 24p3 protein were shown to be (1.5+/-0.2)x10(6) and (3.0+/-0.4)x10(7)M(-1), respectively [15].

Regulatory relationships of Lcn2


Other interactions of Lcn2


Analytical, diagnostic and therapeutic context of Lcn2


  1. Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli infection but not to ischemia-reperfusion injury. Berger, T., Togawa, A., Duncan, G.S., Elia, A.J., You-Ten, A., Wakeham, A., Fong, H.E., Cheung, C.C., Mak, T.W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2. Fischbach, M.A., Lin, H., Zhou, L., Yu, Y., Abergel, R.J., Liu, D.R., Raymond, K.N., Wanner, B.L., Strong, R.K., Walsh, C.T., Aderem, A., Smith, K.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Effects of melatonin and age on gene expression in mouse CNS using microarray analysis. Sharman, E.H., Bondy, S.C., Sharman, K.G., Lahiri, D., Cotman, C.W., Perreau, V.M. Neurochem. Int. (2007) [Pubmed]
  4. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Devireddy, L.R., Gazin, C., Zhu, X., Green, M.R. Cell (2005) [Pubmed]
  5. Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation. Devireddy, L.R., Teodoro, J.G., Richard, F.A., Green, M.R. Science (2001) [Pubmed]
  6. Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. Mishra, J., Mori, K., Ma, Q., Kelly, C., Yang, J., Mitsnefes, M., Barasch, J., Devarajan, P. J. Am. Soc. Nephrol. (2004) [Pubmed]
  7. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Flo, T.H., Smith, K.D., Sato, S., Rodriguez, D.J., Holmes, M.A., Strong, R.K., Akira, S., Aderem, A. Nature (2004) [Pubmed]
  8. Bcr-Abl-mediated suppression of normal hematopoiesis in leukemia. Lin, H., Monaco, G., Sun, T., Ling, X., Stephens, C., Xie, S., Belmont, J., Arlinghaus, R. Oncogene (2005) [Pubmed]
  9. Genetic mapping of the rat Lcn2 gene to chromosome 3. Chen, K., Shepel, L.A., Stoesz, S.P., Brasic, G.M., Gould, M.N. Cytogenet. Cell Genet. (1999) [Pubmed]
  10. Expression of neutrophil gelatinase-associated lipocalin regulates epithelial morphogenesis in vitro. Gwira, J.A., Wei, F., Ishibe, S., Ueland, J.M., Barasch, J., Cantley, L.G. J. Biol. Chem. (2005) [Pubmed]
  11. mRNA expression in mouse hypothalamus and basal forebrain during influenza infection: a novel model for sleep regulation. Ding, M., Toth, L.A. Physiol. Genomics (2006) [Pubmed]
  12. Demonstration of a glycoprotein derived from the 24p3 gene in mouse uterine luminal fluid. Chu, S.T., Huang, H.L., Chen, J.M., Chen, Y.H. Biochem. J. (1996) [Pubmed]
  13. 24p3 in differentiation of myeloid cells. Liu, M., Prisco, M., Drakas, R., Searles, D., Baserga, R. J. Cell. Physiol. (2005) [Pubmed]
  14. An apparent autocrine mechanism amplifies the dexamethasone- and retinoic acid-induced expression of mouse lipocalin-encoding gene 24p3. Garay-Rojas, E., Harper, M., Hraba-Renevey, S., Kress, M. Gene (1996) [Pubmed]
  15. Delivery of ferric ion to mouse spermatozoa is mediated by lipocalin internalization. Elangovan, N., Lee, Y.C., Tzeng, W.F., Chu, S.T. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  16. Phosphorylation of the 24p3 protein secreted from mouse uterus in vitro and in vivo. Lee, Y.C., Lin, S.D., Yu, H.M., Chen, S.T., Chu, S.T. J. Protein Chem. (2001) [Pubmed]
  17. Spermatogonia-dependent expression of testicular genes in mice. Tanaka, K., Tamura, H., Tanaka, H., Katoh, M., Futamata, Y., Seki, N., Nishimune, Y., Hara, T. Dev. Biol. (2002) [Pubmed]
  18. The lipocalin protein family: a role in cell regulation. Flower, D.R. FEBS Lett. (1994) [Pubmed]
  19. Glucocorticoid receptor activation of the Ciz1-Lcn2 locus by long range interactions. Hakim, O., John, S., Ling, J.Q., Biddie, S.C., Hoffman, A.R., Hager, G.L. J. Biol. Chem. (2009) [Pubmed]
  20. SV40-induced expression of mouse gene 24p3 involves a post-transcriptional mechanism. Hraba-Renevey, S., Türler, H., Kress, M., Salomon, C., Weil, R. Oncogene (1989) [Pubmed]
  21. Bacterial colonization of nasal mucosa induces expression of siderocalin, an iron-sequestering component of innate immunity. Nelson, A.L., Barasch, J.M., Bunte, R.M., Weiser, J.N. Cell. Microbiol. (2005) [Pubmed]
  22. Neutrophil gelatinase-associated lipocalin, a siderophore-binding eukaryotic protein. Borregaard, N., Cowland, J.B. Biometals (2006) [Pubmed]
  23. Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction. Hemdahl, A.L., Gabrielsen, A., Zhu, C., Eriksson, P., Hedin, U., Kastrup, J., Thorén, P., Hansson, G.K. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
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