Normal immune system development in mice lacking the Deltex-1 RING finger domain

Mol Cell Biol. 2005 Feb;25(4):1437-45. doi: 10.1128/MCB.25.4.1437-1445.2005.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Antigens, T-Independent / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Flow Cytometry
  • Gene Expression Regulation, Developmental / immunology
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Mutation / genetics
  • Mutation / immunology
  • Sequence Homology, Amino Acid
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Ubiquitin-Protein Ligases

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, T-Independent
  • DNA-Binding Proteins
  • Dtx1 protein, mouse
  • Ubiquitin-Protein Ligases