The Hox11 gene is essential for cell survival during spleen development.
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 beta-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.
Dear
T N
TN
MRC Laboratory of Molecular Biology, Cambridge, UK.
Colledge
W H
WH
Carlton
M B
MB
Lavenir
I
I
Larson
T
T
Smith
A J
AJ
Warren
A J
AJ
Evans
M J
MJ
Sofroniew
M V
MV
Rabbitts
T H
TH
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D015870:Gene Expression; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D015458:Leukemia, T-Cell / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D015345:Oligonucleotide Probes / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics*; D013154:Spleen / Q000002:abnormalities / Q000166:cytology / Q000196:embryology*; D014178:Translocation, Genetic
D018398:Homeodomain Proteins; D015345:Oligonucleotide Probes; D015513:Oncogene Proteins; C487378:Tlx1 protein, mouse