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Gene Review

Lmo4  -  LIM domain only 4

Mus musculus

Synonyms: A730077C12Rik, Breast tumor autoantigen, Crp3, Etohi4, LIM domain only protein 4, ...
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Disease relevance of Lmo4

  • In MCF-7 cells, LMO4 transcripts were upregulated by heregulin, an activator of ErbB receptors that are known to be important in mammary gland development and breast cancer [1].
  • Moreover, in situ hybridization analysis of 177 primary invasive breast carcinomas revealed overexpression of LMO4 in 56% of specimens [2].
  • LMO4 belongs to a family of LIM-only transcriptional regulators, the first two members of which are oncoproteins in acute T cell leukemia [2].
  • Of the peptides analyzed, only RMAD-4 inhibited HIV infectivity at 150 microg/ml, and Crp3 unexpectedly increased HIV replication [3].

High impact information on Lmo4

  • Lmo4 was expressed predominantly in the lobuloalveoli of the mammary gland during pregnancy [2].
  • Overexpression of LMO4 mRNA was observed in 5 of 10 human breast cancer cell lines [2].
  • These studies imply a role for LMO4 in maintaining proliferation of mammary epithelium and suggest that deregulation of this gene may contribute to breast tumorigenesis [2].
  • This factor, referred to as LMO-4, is expressed in overlapping manner with Clim-2 in epidermis and in several other regions, including epithelial cells of the gastrointestinal, respiratory and genitourinary tracts, developing cartilage, pituitary gland, and discrete regions of the central and peripheral nervous system [4].
  • In contrast to Lmo4 nullizygous mice, nonexencephalic Deaf-1 mutants remained healthy [5].

Biological context of Lmo4


Anatomical context of Lmo4

  • Furthermore, fusions of cranial nerves IX and X and defects in cranial nerve V were apparent in some Lmo4(-/-) and Lmo4(+/-) mice [5].
  • Lmo4 is widely expressed in mouse tissues, including adult thymus (mainly CD4, CD8-double positive T cells) and embryonic thymus (mainly CD4, CD8-double negative T cells) [6].
  • The more recently discovered LMO factor LMO4 is highly expressed in proliferating epithelial cells, and frequently overexpressed in breast carcinoma [1].
  • To assess the physiological role of Lmo4 in the mammary gland, we generated conditionally targeted mice lacking Lmo4 in the mammary epithelium during pregnancy [7].
  • High levels of Lmo4 were frequently observed in proliferating cells, such as the crypt cells of the small intestine and the basal cells of the skin and tongue [9].

Associations of Lmo4 with chemical compounds

  • Lmo4 was found to be highly expressed in the proliferating cap cells of the terminal end bud and in the ductal and alveolar luminal cells of the mature mammary gland but was negligible or low in myoepithelial cells [7].
  • Calcium influx via voltage-sensitive calcium channels and NMDA receptors contributes to synaptically induced LMO4-mediated transactivation [10].

Physical interactions of Lmo4

  • Defective neural tube closure and anteroposterior patterning in mice lacking the LIM protein LMO4 or its interacting partner Deaf-1 [5].
  • Targeted deletion of Lmo4 in mice leads to complex phenotypic abnormalities and perinatal lethality [9].

Other interactions of Lmo4


Analytical, diagnostic and therapeutic context of Lmo4


  1. Expression of an engrailed-LMO4 fusion protein in mammary epithelial cells inhibits mammary gland development in mice. Wang, N., Kudryavtseva, E., Ch'en, I.L., McCormick, J., Sugihara, T.M., Ruiz, R., Andersen, B. Oncogene (2004) [Pubmed]
  2. The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer. Visvader, J.E., Venter, D., Hahm, K., Santamaria, M., Sum, E.Y., O'Reilly, L., White, D., Williams, R., Armes, J., Lindeman, G.J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  3. Differential effects on human immunodeficiency virus type 1 replication by alpha-defensins with comparable bactericidal activities. Tanabe, H., Ouellette, A.J., Cocco, M.J., Robinson, W.E. J. Virol. (2004) [Pubmed]
  4. Mouse deformed epidermal autoregulatory factor 1 recruits a LIM domain factor, LMO-4, and CLIM coregulators. Sugihara, T.M., Bach, I., Kioussi, C., Rosenfeld, M.G., Andersen, B. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  5. Defective neural tube closure and anteroposterior patterning in mice lacking the LIM protein LMO4 or its interacting partner Deaf-1. Hahm, K., Sum, E.Y., Fujiwara, Y., Lindeman, G.J., Visvader, J.E., Orkin, S.H. Mol. Cell. Biol. (2004) [Pubmed]
  6. Identification of the LMO4 gene encoding an interaction partner of the LIM-binding protein LDB1/NLI1: a candidate for displacement by LMO proteins in T cell acute leukaemia. Grutz, G., Forster, A., Rabbitts, T.H. Oncogene (1998) [Pubmed]
  7. Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes lobuloalveolar development. Sum, E.Y., Shackleton, M., Hahm, K., Thomas, R.M., O'Reilly, L.A., Wagner, K.U., Lindeman, G.J., Visvader, J.E. Oncogene (2005) [Pubmed]
  8. Two promoters within the human LMO4 gene contribute to its overexpression in breast cancer cells. Wittlin, S., Sum, E.Y., Jonas, N.K., Lindeman, G.J., Visvader, J.E. Genomics (2003) [Pubmed]
  9. The LIM domain protein Lmo4 is highly expressed in proliferating mouse epithelial tissues. Sum, E.Y., O'Reilly, L.A., Jonas, N., Lindeman, G.J., Visvader, J.E. J. Histochem. Cytochem. (2005) [Pubmed]
  10. Calcium activation of the LMO4 transcription complex and its role in the patterning of thalamocortical connections. Kashani, A.H., Qiu, Z., Jurata, L., Lee, S.K., Pfaff, S., Goebbels, S., Nave, K.A., Ghosh, A. J. Neurosci. (2006) [Pubmed]
  11. Identification and characterization of Grainyhead-like epithelial transactivator (GET-1), a novel mammalian Grainyhead-like factor. Kudryavtseva, E.I., Sugihara, T.M., Wang, N., Lasso, R.J., Gudnason, J.F., Lipkin, S.M., Andersen, B. Dev. Dyn. (2003) [Pubmed]
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