Frizzled 9 knock-out mice have abnormal B-cell development

Blood. 2005 Mar 15;105(6):2487-94. doi: 10.1182/blood-2004-06-2334. Epub 2004 Nov 30.

Abstract

The binding of frizzled (Fzd) receptors by their Wnt ligands results in the inhibition of beta-catenin degradation and subsequent transcription of beta-catenin/LEF-inducible genes. The beta-catenin pathway is known to be involved in development, tumorigenesis, and stem cell self-renewal. In humans, the FZD9 gene lies in the region of chromosome 7q11.23 deleted in the neurodevelopmental disorder, Williams-Beuren syndrome (WBS). Fzd9-/- mice show no obvious features of WBS, but reveal a role for Fzd9 in lymphoid development and maturation. Fzd9-/- mice show pronounced splenomegaly, thymic atrophy, and lymphadenopathy with age, with accumulation of plasma cells in lymph nodes. There is a depletion of developing B cells in the bone marrow (BM), particularly in the pre-B stage where immunoglobulin heavy chains are expressed and the cells are undergoing clonal expansion prior to light chain rearrangement. The pre-B defect is partially intrinsic to the hematopoietic system; as in competitive BM reconstitution studies, Fzd9-/- -derived BM exhibits defective B-cell development when implanted into a wild-type host. Mature B cells are present in normal numbers in lymph node and spleen. These findings suggest a role for Fzd9 signaling in lymphoid development, particularly at points where B cells undergo self-renewal prior to further differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrophy / immunology
  • Atrophy / metabolism
  • Atrophy / pathology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Bone Marrow Transplantation
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Chromosomes, Human, Pair 7 / genetics
  • Chromosomes, Human, Pair 7 / immunology
  • Frizzled Receptors
  • Humans
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light Chains / immunology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphatic Diseases / immunology
  • Lymphatic Diseases / metabolism
  • Lymphatic Diseases / pathology
  • Lymphopoiesis / genetics
  • Lymphopoiesis / immunology*
  • Mice
  • Mice, Knockout
  • Receptors, Neurotransmitter / genetics
  • Receptors, Neurotransmitter / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Somatic Hypermutation, Immunoglobulin / genetics
  • Somatic Hypermutation, Immunoglobulin / immunology
  • Spleen / immunology
  • Spleen / metabolism
  • Spleen / pathology
  • TCF Transcription Factors / immunology
  • TCF Transcription Factors / metabolism
  • Thymus Gland / immunology
  • Thymus Gland / metabolism
  • Thymus Gland / pathology
  • Williams Syndrome / genetics
  • Williams Syndrome / immunology
  • Williams Syndrome / metabolism
  • Williams Syndrome / pathology
  • beta Catenin / biosynthesis
  • beta Catenin / immunology

Substances

  • Frizzled Receptors
  • Fzd9 protein, mouse
  • Immunoglobulin Light Chains
  • Receptors, Neurotransmitter
  • TCF Transcription Factors
  • beta Catenin