Normal immune system development in mice lacking the Deltex-1 RING finger domain.
The Notch signaling pathway controls several cell fate decisions during lymphocyte development, from T-cell lineage commitment to the peripheral differentiation of B and T lymphocytes. Deltex-1 is a RING finger ubiquitin ligase which is conserved from Drosophila to humans and has been proposed to be a regulator of Notch signaling. Its pattern of lymphoid expression as well as gain-of-function experiments suggest that Deltex-1 regulates both B-cell lineage and splenic marginal-zone B-cell commitment. Deltex-1 was also found to be highly expressed in germinal-center B cells. To investigate the physiological function of Deltex-1, we generated a mouse strain lacking the Deltex-1 RING finger domain, which is essential for its ubiquitin ligase activity. Deltex-1(Delta/Delta) mice were viable and fertile. A detailed histological analysis did not reveal any defects in major organs. T- and B-cell development was normal, as were humoral responses against T-dependent and T-independent antigens. These data indicate that the Deltex-1 ubiquitin ligase activity is dispensable for mouse development and immune function. Possible compensatory mechanisms, in particular those from a fourth Deltex gene identified during the course of this study, are also discussed.
Storck
Sébastien
S
INSERM U373, Faculté de Médecine Necker-Enfants Malades, 75730 Paris, France.
Delbos
Frédéric
F
Stadler
Nicolas
N
Thirion-Delalande
Catherine
C
Bernex
Florence
F
Verthuy
Christophe
C
Ferrier
Pierre
P
Weill
Jean-Claude
JC
Reynaud
Claude-Agnès
CA
D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D044767:Ubiquitin-Protein Ligases
D000945:Antigens, Differentiation, T-Lymphocyte; D000955:Antigens, T-Independent; D004268:DNA-Binding Proteins; C104035:Dtx1 protein, mouse; D044767:Ubiquitin-Protein Ligases