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

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.

Pubmed ID: 15572594


  • Ranheim EA
  • Kwan HC
  • Reya T
  • Wang YK
  • Weissman IL
  • Francke U



Publication Data

March 15, 2005

Associated Grants

  • Agency: PHS HHS, Id: K08-90450
  • Agency: NICHD NIH HHS, Id: R01 HD39921
  • Agency: NIGMS NIH HHS, Id: T32 GM08748

Mesh Terms

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