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Gene Review

Ltf  -  lactotransferrin

Mus musculus

Synonyms: Csp82, Lactoferrin, Lactotransferrin, Lf, MMS10R, ...
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Disease relevance of Ltf

  • The structure and nucleotide sequence of the murine lactotransferrin-encoding gene (LTF) deduced partly by direct sequencing of genomic clones in the lambda phage vector and partly by enzymatic amplification of genomic DNA segments primed with the oligodeoxyribonucleotide primers homologous to the cDNA sequence [1].
  • To further define these properties of Lf, we have investigated the response to Staphylococcus aureus infection in transgenic mice carrying a functional human Lf gene [2].
  • A tissue-specific regulatory sequence was critical for the establishment of lactoferrin expression in human endometrium carcinoma cells, but not in rat glioma cells located between -1739 and -922 [3].
  • To confirm that these effects of Lf transgene expression could occur in the absence of live bacterial infection, we also showed that Lf-transgenic DBA/1 mice exhibited enhanced severity of collagen-induced arthritis, an established model of Th1-induced articular inflammation [2].
  • A series of different lengths of the mouse lactoferrin gene 5' flanking region were linked to a chloramphenicol acetyltransferase (CAT) reporter construct and transfected into human endometrial carcinoma HEC-1B cells, an estrogen receptor null cell line, in order to examine the methoxychlor response [4].

High impact information on Ltf


Chemical compound and disease context of Ltf


Biological context of Ltf


Anatomical context of Ltf


Associations of Ltf with chemical compounds

  • We previously demonstrated that the estrogen response module (mERM) of the mouse lactoferrin gene, which contains an overlapping chicken ovalbumin upstream promoter transcription factor (COUP-TF)- and estrogen receptor-binding element, is responsible for estrogen induction [16].
  • Lactoferrin, an iron-binding glycoprotein, kills bacteria and modulates inflammatory and immune responses [17].
  • Lactoferrin (Lf), a ferric ion (Fe3+)-binding glycoprotein, is found most notably in milk, probably to mediate protection against microbial infection of the mammary gland [18].
  • We report here the sequence of a caprine LTF cDNA, 2411 bp in length, encoding the pre-protein (709 amino acid residues) [19].
  • Lactoferrin was labeled with 125I by the chloramine-T method to yield a product having 20 muCi/mug protein and an isotope incorporation of 0.6 atoms of 125I per molecule [20].

Regulatory relationships of Ltf

  • Pre-injection of lactoferrin into normal mice inhibited the plasma clearance of both non-lipolyzed chylomicrons and chylomicrons lipolyzed by HL [21].
  • Recombinant lactoferrin stimulated procaspase-3 processing at 10(-6)-10(-7)M to an extent similar to that by granzyme B in vitro [22].
  • Fetal mouse liver cultures capable of producing both erythropoietin (Ep) and granulocyte-macrophage colony stimulating activity (GM-CSA) were used to study the specificity of lactoferrin as an inhibitor of the production of GM-CSA [23].

Other interactions of Ltf


Analytical, diagnostic and therapeutic context of Ltf


  1. Structure of the murine lactotransferrin gene is similar to the structure of other transferrin-encoding genes and shares a putative regulatory region with the murine myeloperoxidase gene. Shirsat, N.V., Bittenbender, S., Kreider, B.L., Rovera, G. Gene (1992) [Pubmed]
  2. Enhanced Th1 response to Staphylococcus aureus infection in human lactoferrin-transgenic mice. Guillén, C., McInnes, I.B., Vaughan, D.M., Kommajosyula, S., Van Berkel, P.H., Leung, B.P., Aguila, A., Brock, J.H. J. Immunol. (2002) [Pubmed]
  3. Characterization of estrogen-responsive mouse lactoferrin promoter. Liu, Y.H., Teng, C.T. J. Biol. Chem. (1991) [Pubmed]
  4. Methoxychlor stimulates the mouse lactoferrin gene promoter through a GC-rich element. Zhang, Z., Teng, C.T. Biochem. Cell Biol. (2002) [Pubmed]
  5. Correction of the iron overload defect in beta-2-microglobulin knockout mice by lactoferrin abolishes their increased susceptibility to tuberculosis. Schaible, U.E., Collins, H.L., Priem, F., Kaufmann, S.H. J. Exp. Med. (2002) [Pubmed]
  6. Remnant lipoproteins inhibit malaria sporozoite invasion of hepatocytes. Sinnis, P., Willnow, T.E., Briones, M.R., Herz, J., Nussenzweig, V. J. Exp. Med. (1996) [Pubmed]
  7. Regulation of macrophage and granulocyte proliferation. Specificities of prostaglandin E and lactoferrin. Pelus, L.M., Broxmeyer, H.E., Kurland, J.I., Moore, M.A. J. Exp. Med. (1979) [Pubmed]
  8. Release of lactoferrin by polymorphonuclear leukocytes after aerosol challenge with Escherichia coli. LaForce, F.M., Boose, D.S. Infect. Immun. (1987) [Pubmed]
  9. Inability to detect mycobactin in mycobacteria-infected tissues suggests an alternative iron acquisition mechanism by mycobacteria in vivo. Lambrecht, R.S., Collins, M.T. Microb. Pathog. (1993) [Pubmed]
  10. Lactoferrin effects of phagocytic cell function. II. The presence of iron is required for the lactoferrin molecule to stimulate intracellular killing by macrophages but not to enhance the uptake of particles and microorganisms. Lima, M.F., Kierszenbaum, F. J. Immunol. (1987) [Pubmed]
  11. Comparative effects in vivo of recombinant murine interleukin 3, natural murine colony-stimulating factor-1, and recombinant murine granulocyte-macrophage colony-stimulating factor on myelopoiesis in mice. Broxmeyer, H.E., Williams, D.E., Cooper, S., Shadduck, R.K., Gillis, S., Waheed, A., Urdal, D.L., Bicknell, D.C. J. Clin. Invest. (1987) [Pubmed]
  12. Downregulation of lactoferrin by PPARalpha ligands: role in perturbation of hepatocyte proliferation and apoptosis. Hasmall, S., Orphanides, G., James, N., Pennie, W., Hedley, K., Soames, A., Kimber, I., Roberts, R. Toxicol. Sci. (2002) [Pubmed]
  13. Bovine plasma proteins increase virulence of Haemophilus somnus in mice. Geertsema, R.S., Kimball, R.A., Corbeil, L.B. Microb. Pathog. (2007) [Pubmed]
  14. The ingestion and digestion of human lactoferrin by mouse peritoneal macrophages and the transfer of its iron into ferritin. van Snick, J.L., Markowetz, B., Masson, P.L. J. Exp. Med. (1977) [Pubmed]
  15. Oral administration of lactoferrin increases NK cell activity in mice via increased production of IL-18 and type I IFN in the small intestine. Kuhara, T., Yamauchi, K., Tamura, Y., Okamura, H. J. Interferon Cytokine Res. (2006) [Pubmed]
  16. COUP-TF acts as a competitive repressor for estrogen receptor-mediated activation of the mouse lactoferrin gene. Liu, Y., Yang, N., Teng, C.T. Mol. Cell. Biol. (1993) [Pubmed]
  17. Differential expression and estrogen response of lactoferrin gene in the female reproductive tract of mouse, rat, and hamster. Teng, C.T., Beard, C., Gladwell, W. Biol. Reprod. (2002) [Pubmed]
  18. Structure of the bovine lactoferrin-encoding gene and its promoter. Seyfert, H.M., Tuckoricz, A., Interthal, H., Koczan, D., Hobom, G. Gene (1994) [Pubmed]
  19. Characterization of the goat lactoferrin cDNA: assignment of the relevant locus to bovine U12 synteny group. Le Provost, F., Nocart, M., Guerin, G., Martin, P. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  20. Radioimmunoassay for murine lactoferrin, a protein marker of myeloid and mammary epithelial secretory cell differentiation. Segars, F.M., Kinkade, J.M. J. Immunol. Methods (1977) [Pubmed]
  21. Plasma clearance and liver uptake of chylomicron remnants generated by hepatic lipase lipolysis: evidence for a lactoferrin-sensitive and apolipoprotein E-independent pathway. Crawford, S.E., Borensztajn, J. J. Lipid Res. (1999) [Pubmed]
  22. A novel apoptosis cascade mediated by lysosomal lactoferrin and its participation in hepatocyte apoptosis induced by D-galactosamine. Katunuma, N., Le, Q.T., Murata, E., Matsui, A., Majima, E., Ishimaru, N., Hayashi, Y., Ohashi, A. FEBS Lett. (2006) [Pubmed]
  23. Specificity of lactoferrin as an inhibitor of granulocyte-macrophage colony-stimulating activity production from fetal mouse liver cells. Zucali, J.R., Broxmeyer, H.E., Ulatowski, J.A. Blood (1979) [Pubmed]
  24. Antioxidant and antibacterial genes are upregulated in early involution of the mouse mammary gland: sharp increase of ceruloplasmin and lactoferrin in accumulating breast milk. Nakamura, M., Tomita, A., Nakatani, H., Matsuda, T., Nadano, D. DNA Cell Biol. (2006) [Pubmed]
  25. Identification of a series of differentiation-associated gene sequences from GM-CSF stimulated bone marrow. Moscinski, L.C., Prystowsky, M.B. Oncogene (1990) [Pubmed]
  26. Lactotransferrin is the major estrogen inducible protein of mouse uterine secretions. Pentecost, B.T., Teng, C.T. J. Biol. Chem. (1987) [Pubmed]
  27. Identification of lactoferrin as the granulocyte-derived inhibitor of colony-stimulating activity production. Broxmeyer, H.E., Smithyman, A., Eger, R.R., Meyers, P.A., de Sousa, M. J. Exp. Med. (1978) [Pubmed]
  28. Iron status in mice carrying a targeted disruption of lactoferrin. Ward, P.P., Mendoza-Meneses, M., Cunningham, G.A., Conneely, O.M. Mol. Cell. Biol. (2003) [Pubmed]
  29. Assignment of the lactotransferrin gene to human chromosome 3 and to mouse chromosome 9. Teng, C.T., Pentecost, B.T., Marshall, A., Solomon, A., Bowman, B.H., Lalley, P.A., Naylor, S.L. Somat. Cell Mol. Genet. (1987) [Pubmed]
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