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Gene Review

Tlx1  -  T cell leukemia, homeobox 1

Mus musculus

Synonyms: Homeobox TLX-1, Homeobox protein Hox-11, Hox-11, Hox11, T-cell leukemia homeobox protein 1, ...
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Disease relevance of Tlx1

  • Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis and hyperganglionic megacolon, respectively [1].
  • These data establish the t(5;14)(q35;q32) as a major abnormality, and Hox11 family member activation as an important pathway in T ALL leukemogenesis [2].
  • As Hoxll can function as a transcription factor, we examined the spatial and temporal mRNA expression patterns of Hox11 and a candidate target gene, the Wilm's tumor gene Wt1, in the developing spleen [3].

High impact information on Tlx1


Biological context of Tlx1


Anatomical context of Tlx1

  • Tbx1 is also required for normal expression of Tlx1 and Fgf10 in pharyngeal mesoderm, in addition to correct neural crest cell patterning in the mandibular arch [11].
  • Pbx1 and Hox11 genetically interact in spleen formation and loss of either is associated with a similar reduction of progenitor cell proliferation and failed expansion of the splenic anlage [12].
  • Neither Hox11L1 nor Hox11L2 was expressed in the branchial arches or their motor nuclei within wild-type or Hox11-/- mice [13].
  • Additionally, Hox11 is expressed in the surface ectoderm of the first branchial arch in the region destined to become the tongue and teeth and then in ganglia innervating this area [13].
  • In Hox11-/-<-->+/+ chimaeras, spleens were devoid of Hox11(-/-) cells, indicating that the genetic defect is cell autonomous and not due to failure of the organ anlage to attract and retain haematopoietic cells [14].

Other interactions of Tlx1

  • Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates [6].
  • These studies establish a Pbx1-Hox11-dependent genetic and transcriptional pathway in spleen ontogeny [12].
  • As described in this study, removal of the last Hox11 paralogous member, Hoxc11, results in the complete loss of metanephric kidney induction [15].
  • On the key role of secondary lymphoid organs in antiviral immune responses studied in alymphoplastic (aly/aly) and spleenless (Hox11(-)/-) mutant mice [16].
  • Hox11 is required to maintain normal Wt1 mRNA levels in the developing spleen [3].

Analytical, diagnostic and therapeutic context of Tlx1


  1. Rnx deficiency results in congenital central hypoventilation. Shirasawa, S., Arata, A., Onimaru, H., Roth, K.A., Brown, G.A., Horning, S., Arata, S., Okumura, K., Sasazuki, T., Korsmeyer, S.J. Nat. Genet. (2000) [Pubmed]
  2. A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia. Bernard, O.A., Busson-LeConiat, M., Ballerini, P., Mauchauffé, M., Della Valle, V., Monni, R., Nguyen Khac, F., Mercher, T., Penard-Lacronique, V., Pasturaud, P., Gressin, L., Heilig, R., Daniel, M.T., Lessard, M., Berger, R. Leukemia (2001) [Pubmed]
  3. Hox11 is required to maintain normal Wt1 mRNA levels in the developing spleen. Koehler, K., Franz, T., Dear, T.N. Dev. Dyn. (2000) [Pubmed]
  4. Hox11 controls the genesis of the spleen. Roberts, C.W., Shutter, J.R., Korsmeyer, S.J. Nature (1994) [Pubmed]
  5. Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1. Qian, Y., Shirasawa, S., Chen, C.L., Cheng, L., Ma, Q. Genes Dev. (2002) [Pubmed]
  6. Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates. Cheng, L., Arata, A., Mizuguchi, R., Qian, Y., Karunaratne, A., Gray, P.A., Arata, S., Shirasawa, S., Bouchard, M., Luo, P., Chen, C.L., Busslinger, M., Goulding, M., Onimaru, H., Ma, Q. Nat. Neurosci. (2004) [Pubmed]
  7. Cig30 and Pitx3 genes are arranged in a partially overlapping tail-to-tail array resulting in complementary transcripts. Tvrdik, P., Asadi, A., Kozak, L.P., Nuglozeh, E., Parente, F., Nedergaard, J., Jacobsson, A. J. Biol. Chem. (1999) [Pubmed]
  8. The basic helix-loop-helix transcription factor capsulin controls spleen organogenesis. Lu, J., Chang, P., Richardson, J.A., Gan, L., Weiler, H., Olson, E.N. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  9. Genetic mapping of two mouse homeobox genes Tlx-1 and Tlx-2 to murine chromosomes 19 and 6. Wen, X.Y., Tang, S., Breitman, M.L. Genomics (1994) [Pubmed]
  10. The T-cell oncogenic protein HOX11 activates Aldh1 expression in NIH 3T3 cells but represses its expression in mouse spleen development. Greene, W.K., Bahn, S., Masson, N., Rabbitts, T.H. Mol. Cell. Biol. (1998) [Pubmed]
  11. The del22q11.2 candidate gene Tbx1 regulates branchiomeric myogenesis. Kelly, R.G., Jerome-Majewska, L.A., Papaioannou, V.E. Hum. Mol. Genet. (2004) [Pubmed]
  12. A Pbx1-dependent genetic and transcriptional network regulates spleen ontogeny. Brendolan, A., Ferretti, E., Salsi, V., Moses, K., Quaggin, S., Blasi, F., Cleary, M.L., Selleri, L. Development (2005) [Pubmed]
  13. Development expression of Hox11 and specification of splenic cell fate. Roberts, C.W., Sonder, A.M., Lumsden, A., Korsmeyer, S.J. Am. J. Pathol. (1995) [Pubmed]
  14. Hox11 acts cell autonomously in spleen development and its absence results in altered cell fate of mesenchymal spleen precursors. Kanzler, B., Dear, T.N. Dev. Biol. (2001) [Pubmed]
  15. Hox11 paralogous genes are essential for metanephric kidney induction. Wellik, D.M., Hawkes, P.J., Capecchi, M.R. Genes Dev. (2002) [Pubmed]
  16. On the key role of secondary lymphoid organs in antiviral immune responses studied in alymphoplastic (aly/aly) and spleenless (Hox11(-)/-) mutant mice. Karrer, U., Althage, A., Odermatt, B., Roberts, C.W., Korsmeyer, S.J., Miyawaki, S., Hengartner, H., Zinkernagel, R.M. J. Exp. Med. (1997) [Pubmed]
  17. Two forms of Hox11 a T cell leukemia oncogene, are expressed in fetal spleen but not in primary lymphocytes. Yamamoto, H., Hatano, M., Iitsuka, Y., Mahyar, N.S., Yamamoto, M., Tokuhisa, T. Mol. Immunol. (1995) [Pubmed]
  18. Early steps in the evolution of multicellularity: deep structural and functional homologies among homeobox genes in sponges and higher metazoans. Coutinho, C.C., Fonseca, R.N., Mansure, J.J., Borojevic, R. Mech. Dev. (2003) [Pubmed]
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