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Gene Review

Hoxd3  -  homeobox D3

Mus musculus

Synonyms: Homeobox protein Hox-4.1, Homeobox protein Hox-D3, Homeobox protein MH-19, Hox-4.1, Hox-5.5, ...
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Disease relevance of Hoxd3

  • 1. The jumping endpoint lies within genomic clones from a lambda phage walk extending from the 5' end of Hox-4.1, and thus provides clear evidence of linkage between the two Hox loci [1].
  • We now show that there is a deletion of one copy of the Hox-4.1 homeobox gene in the myeloid leukemias with this deletion in chromosome 2 [2].

High impact information on Hoxd3


Biological context of Hoxd3


Anatomical context of Hoxd3

  • Hoxb3, Hoxd3 double mutants show no obvious defects in the thymus or parathyroids [9].
  • This unique function may be conferred by the expression of Hoxa3, but not Hoxb3 nor Hoxd3, in the pharyngeal pouch endoderm [9].
  • Mice homozygous for a targeted disruption of Hoxd-3 (Hox-4.1) exhibit anterior transformations of the first and second cervical vertebrae, the atlas and the axis [5].
  • Hoxd-3 expression was observed from 8.5 days p.c., in the neural tube with a sharp border in the hind brain at the level of rhombomeres 4-5 [10].

Other interactions of Hoxd3

  • Previous analysis has shown that although mice homozygous for loss-of-function mutations in either Hoxa3 or Hoxd3 have no defects in common, mice mutant for both genes demonstrate that these two genes strongly interact in a dosage-dependent manner [11].
  • Our results demonstrate that Hox-4.1 lies approximately 35 kb downstream of the Hox-5.1 gene and that the two loci do indeed thus constitute parts of the same HOX complex [1].

Analytical, diagnostic and therapeutic context of Hoxd3

  • Paralogous Hox genes, such as Hoxa3, Hoxb3 and Hoxd3, generally have very similar patterns of expression, and gene targeting experiments have shown that members of paralogy group 3 can functionally compensate for each other [12].
  • Northern blot analysis of RNA from 8- to 11-day-old mouse embryos revealed a 4.3-kb species of Hoxd-3 RNA, whereas a less abundant 3.0-kb species of Hoxd-3 RNA was found in RNA from 9- to 11-day-old embryos [4].


  1. The murine genes Hox-5.1 and Hox-4.1 belong to the same HOX complex on chromosome 2. Stubbs, L., Poustka, A., Baron, A., Lehrach, H., Lonai, P., Duboule, D. Genomics (1990) [Pubmed]
  2. Deletion of a homeobox gene in myeloid leukemias with a deletion in chromosome 2. Blatt, C., Sachs, L. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  3. Maintenance of functional equivalence during paralogous Hox gene evolution. Greer, J.M., Puetz, J., Thomas, K.R., Capecchi, M.R. Nature (2000) [Pubmed]
  4. Sequence and expression of the murine Hoxd-3 homeobox gene. Tan, D.P., Shao, X., Pu, L., Guo, V., Nirenberg, M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  5. Mice homozygous for a targeted disruption of Hoxd-3 (Hox-4.1) exhibit anterior transformations of the first and second cervical vertebrae, the atlas and the axis. Condie, B.G., Capecchi, M.R. Development (1993) [Pubmed]
  6. Chromosome assignment of the murine Hox-4.1 gene. Pravtcheva, D., Newman, M., Hunihan, L., Lonai, P., Ruddle, F.H. Genomics (1989) [Pubmed]
  7. The nucleotide sequence of the murine Hox-D3 (Hox-4.1) gene reveals extensive identity with the human protein. Brown, W.M., Zhou, L., Taylor, G.R. Biochim. Biophys. Acta (1994) [Pubmed]
  8. Identification and expression of a regeneration-specific homeobox gene in the newt limb blastema. Brown, R., Brockes, J.P. Development (1991) [Pubmed]
  9. Hox group 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands. Manley, N.R., Capecchi, M.R. Dev. Biol. (1998) [Pubmed]
  10. Analysis of the Hoxd-3 gene: structure and localization of its sense and natural antisense transcripts. Bedford, M., Arman, E., Orr-Urtreger, A., Lonai, P. DNA Cell Biol. (1995) [Pubmed]
  11. Hox group 3 paralogous genes act synergistically in the formation of somitic and neural crest-derived structures. Manley, N.R., Capecchi, M.R. Dev. Biol. (1997) [Pubmed]
  12. Independent regulation of initiation and maintenance phases of Hoxa3 expression in the vertebrate hindbrain involve auto- and cross-regulatory mechanisms. Manzanares, M., Bel-Vialar, S., Ariza-McNaughton, L., Ferretti, E., Marshall, H., Maconochie, M.M., Blasi, F., Krumlauf, R. Development (2001) [Pubmed]
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