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Gene Review

Hoxa11  -  homeobox A11

Mus musculus

Synonyms: Homeobox protein Hox-1.9, Homeobox protein Hox-A11, Hox-1.9, Hoxa-11
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Disease relevance of Hoxa11

  • Furthermore, targeted mutation of Hoxa 11 is shown to result in both male and female sterility [1].
  • Furthermore, while the reproductive tracts of Hoxa-10 and Hoxa-11 single heterozygous mutants of both sexes were primarily unaffected, male transheterozygotes displayed cryptorchidism and abnormal tortuosity of the ductus deferens, and female transheterozygotes exhibited abnormal uterotubal junctions and narrowing of the uterus [2].
  • Clonal cell lines representing different developmental stages of the metanephric mesenchyme were made from transgenic mice with the Simian Virus 40 T-antigen (SV40 Tag) gene driven by the Hoxa 11 promoter [3].
  • PURPOSE: We investigated whether infertility could be reversed in cryptorchid mice (with disrupted expression of the homeobox gene Hoxa 11) by orchiopexy and mating such animals with females of proven fertility [4].

High impact information on Hoxa11

  • In addition, Hox group 11-dependent vertebral sacralization requires Hoxa11 expression in the presomitic mesoderm, while their caudal differentiation requires that Hoxa11 is expressed in the somites [5].
  • Hoxa11/Hoxd11 double mutants, however, demonstrate hypoplasia of the kidneys [6].
  • Hoxa 11 is upstream of Integrin alpha8 expression in the developing kidney [7].
  • To this end, we conducted a screen for Hoxa 11-responsive genes in two kidney cell lines [7].
  • The Integrin alpha8 gene is expressed together with Hoxa 11 in metanephric mesenchyme cells, and mutation of Integrin alpha8 gives a bud-branching morphogenesis defect very similar to that observed in Hoxa 11/Hoxd 11 mutant mice [7].

Biological context of Hoxa11


Anatomical context of Hoxa11

  • By immunohistochemical analysis, Hoxa11 expression is restricted to the early metanephric mesenchyme, which induces ureteric bud formation and branching [12].
  • In this study, we show that malformation of the forelimb zeugopod in Hoxa11/Hoxd11 double mutants is a consequence of interruption at multiple steps during the formation of the radius and ulna [13].
  • In this report, we describe potential altered cellular processes in the developing uterus of Hoxa11 mutants [8].
  • Hoxa11 regulates stromal cell death and proliferation during neonatal uterine development [8].
  • Here, we focus on two Abd-B-type genes, Hoxa-10 and Hoxa-11, which are coexpressed in developing vertebrae, limbs, and reproductive tracts [2].

Associations of Hoxa11 with chemical compounds

  • These results demonstrate that the Hoxa-11 gene is required for normal uterine stromal cell and glandular differentiation during pregnancy, as is the presence of the steroid-induced glandular LIF burst initiating embryo implantation [14].
  • Repressor domain and nuclear localization signal of the murine Hoxa-11 protein are located in the homeodomain: no evidence for role of poly alanine stretches in transcriptional repression [15].

Physical interactions of Hoxa11

  • Analyses of animals homozygous for the HoxDRXI mutant allele revealed the function of this region in controlling Hoxd-12 expression in the presumptive posterior zeugopod where it genetically interacts with Hoxa-11 [16].

Regulatory relationships of Hoxa11


Other interactions of Hoxa11

  • The displacement of this domain toward the tip of the limb during development suggests that Hox-1.8 and Hox-1.9 were expressed in muscle precursor cells which migrate into the limb [19].
  • Histologic analysis demonstrates normal uterine morphology in Hoxa11 mutants as compared with controls at the newborn stage and d 7 after birth [8].
  • These findings suggest that Hoxa11 is required for proper cellular proliferation and apoptotic responses in the developing neonatal uterus and that the regulation of epidermal growth factor receptor is critical to these processes [8].
  • Thus, MLL-ENL is required to initiate and maintain immortalization of myeloid progenitors and may contribute to leukemogenesis by aberrantly sustaining the expression of a "Hox code" consisting of Hoxa4 to Hoxa11 [20].
  • Furthermore, the mRNA expression levels of Hoxa 11 and steroidogenic factor-1 (SF-1) were determined as a marker for fetal development [11].

Analytical, diagnostic and therapeutic context of Hoxa11


  1. Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility. Hsieh-Li, H.M., Witte, D.P., Weinstein, M., Branford, W., Li, H., Small, K., Potter, S.S. Development (1995) [Pubmed]
  2. Characterization of Hoxa-10/Hoxa-11 transheterozygotes reveals functional redundancy and regulatory interactions. Branford, W.W., Benson, G.V., Ma, L., Maas, R.L., Potter, S.S. Dev. Biol. (2000) [Pubmed]
  3. Microarray analysis of novel cell lines representing two stages of metanephric mesenchyme differentiation. Valerius, M.T., Patterson, L.T., Witte, D.P., Potter, S.S. Mech. Dev. (2002) [Pubmed]
  4. Early orchiopexy restores fertility in the Hoxa 11 gene knockout mouse. Lewis, A.G., Pecha, B.R., Smith, E.P., Gardner, B.J., Hsieh-Li, H.M., Potter, S.S., Sheldon, C.A. J. Urol. (2003) [Pubmed]
  5. Hox genes specify vertebral types in the presomitic mesoderm. Carapuço, M., Nóvoa, A., Bobola, N., Mallo, M. Genes Dev. (2005) [Pubmed]
  6. Hox11 paralogous genes are essential for metanephric kidney induction. Wellik, D.M., Hawkes, P.J., Capecchi, M.R. Genes Dev. (2002) [Pubmed]
  7. Hoxa 11 is upstream of Integrin alpha8 expression in the developing kidney. Valerius, M.T., Patterson, L.T., Feng, Y., Potter, S.S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. Hoxa11 regulates stromal cell death and proliferation during neonatal uterine development. Wong, K.H., Wintch, H.D., Capecchi, M.R. Mol. Endocrinol. (2004) [Pubmed]
  9. Comprehensive microarray analysis of Hoxa11/Hoxd11 mutant kidney development. Schwab, K., Hartman, H.A., Liang, H.C., Aronow, B.J., Patterson, L.T., Potter, S.S. Dev. Biol. (2006) [Pubmed]
  10. Functional comparison of the Hoxa 4, Hoxa 10, and Hoxa 11 homeoboxes. Zhao, Y., Potter, S.S. Dev. Biol. (2002) [Pubmed]
  11. Effect of prenatal exposure to diethylstilbestrol on Müllerian duct development in fetal male mice. Visser, J.A., McLuskey, A., Verhoef-Post, M., Kramer, P., Grootegoed, J.A., Themmen, A.P. Endocrinology (1998) [Pubmed]
  12. Hoxa11 and Hoxd11 regulate branching morphogenesis of the ureteric bud in the developing kidney. Patterson, L.T., Pembaur, M., Potter, S.S. Development (2001) [Pubmed]
  13. Multiple roles of Hoxa11 and Hoxd11 in the formation of the mammalian forelimb zeugopod. Boulet, A.M., Capecchi, M.R. Development (2004) [Pubmed]
  14. Abnormal uterine stromal and glandular function associated with maternal reproductive defects in Hoxa-11 null mice. Gendron, R.L., Paradis, H., Hsieh-Li, H.M., Lee, D.W., Potter, S.S., Markoff, E. Biol. Reprod. (1997) [Pubmed]
  15. Repressor domain and nuclear localization signal of the murine Hoxa-11 protein are located in the homeodomain: no evidence for role of poly alanine stretches in transcriptional repression. Roth, J.J., Breitenbach, M., Wagner, G.P. J. exp. zool. B. Mol. Dev. Evol. (2005) [Pubmed]
  16. Genetic analysis of a Hoxd-12 regulatory element reveals global versus local modes of controls in the HoxD complex. Hérault, Y., Beckers, J., Kondo, T., Fraudeau, N., Duboule, D. Development (1998) [Pubmed]
  17. Functional equivalence and rescue among group 11 Hox gene products in vertebral patterning. Zákány, J., Gérard, M., Favier, B., Potter, S.S., Duboule, D. Dev. Biol. (1996) [Pubmed]
  18. Hoxa-11 and Hoxa-13 are involved in repression of MyoD during limb muscle development. Yamamoto, M., Kuroiwa, A. Dev. Growth Differ. (2003) [Pubmed]
  19. The establishment of murine Hox-1 expression domains during patterning of the limb. Haack, H., Gruss, P. Dev. Biol. (1993) [Pubmed]
  20. Continuous MLL-ENL expression is necessary to establish a "Hox Code" and maintain immortalization of hematopoietic progenitor cells. Horton, S.J., Grier, D.G., McGonigle, G.J., Thompson, A., Morrow, M., De Silva, I., Moulding, D.A., Kioussis, D., Lappin, T.R., Brady, H.J., Williams, O. Cancer Res. (2005) [Pubmed]
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