The Hox11 gene is essential for cell survival during spleen development

Terence Neil Dear, W. H. Colledge, M. B.L. Carlton, I. Lavenir, T. Larson, A. J.H. Smith, A. J. Warren, M. J. Evans, M. V. Sofroniew, T. H. Rabbitts

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154 Citations (Scopus)

Abstract

The HOX11 homeobox gene was identified via the translocation t(10;14) in T cell leukaemia. To determine the function of this gene in mice, null mutations were made using homologous recombination in ES cells to incorporate lacZ into the hox11 transcription unit. Production of β-galactosidase from the recombinant hox11 allele in +/- mutants allowed identification of sites of hox11 expression which included the developing spleen. Newborn hox11 -/- mice exhibit asplenia. Spleen formation commences normally at E11.5 in hox11 -/- mutant embryos but the spleen anlage undergoes rapid and complete resorption between E12.5 and E13.5. Dying spleen cells exhibit molecular features of apoptosis, suggesting that programmed cell death is initiated at this stage of organ development in the absence of hox11 protein. Thus hox11 is not required to initiate spleen development but is essential for the survival of splenic precursors during organogenesis. This function for hox11 suggests that enhanced cell survival may result from the t(10;14) which activates HOX11 in T cell leukaemias, further strengthening the association between oncogene-induced cell survival and tumorigenesis.

Original languageEnglish
Pages (from-to)2909-2915
Number of pages7
JournalDevelopment
Volume121
Issue number9
Publication statusPublished - 1 Jan 1995

Keywords

  • Apoptosis
  • Asplenia
  • Cancer
  • Homeodomain
  • Hox11
  • Human
  • Leukaemia
  • Mouse
  • Translocation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Dear, T. N., Colledge, W. H., Carlton, M. B. L., Lavenir, I., Larson, T., Smith, A. J. H., ... Rabbitts, T. H. (1995). The Hox11 gene is essential for cell survival during spleen development. Development, 121(9), 2909-2915.