Molecular Characterisation of Three Murine HOX11-Related Homeobox Genes, Tlx-1, -2, and -3, and Restricted Expression of Tlx-1 during Embryogenesis: (murine/homeobox/cloning/motif/expression).

Abstract

Elevated expression of the human homeobox gene HOX11 has been implicated in T cell acute lymphoblastic leukemia. We report here the isolation and characterisation of three murine genes, Tlx-1, -2, and -3, which are related to HOX11 and constitute a new class of homeobox genes. Sequence analysis indicates that Tlx-1 is a murine homolog of HOX11. The expression during development of Tlx-1 was studied by in situ hybridization. Tlx-1 expression was found in the first branchial arch, the pancreas, the hindbrain and the epidermis of the ear of the developing embryos. Localized expression of Tlx-1 in these developing structures suggests that it might play a specific role during post-implantation development and its aberrant expression might be involved in oncogenesis. The homeodomains of Tlx-2 and -3 are found to be 75% and 80% identical to that of Tlx-1, respectively. In addition to the homeodomain, the three Tlx proteins also share four conserved motifs (TH1-TH4). Interestingly, these motifs are also found in other developmental control genes and transcription factors, suggesting a functional role in transcriptional regulation.