| First Author | Ranheim EA | Year | 2005 |
| Journal | Blood | Volume | 105 |
| Issue | 6 | Pages | 2487-94 |
| PubMed ID | 15572594 | Mgi Jnum | J:98133 |
| Mgi Id | MGI:3577530 | Doi | 10.1182/blood-2004-06-2334 |
| Citation | Ranheim EA, et al. (2005) Frizzled 9 knock-out mice have abnormal B-cell development. Blood 105(6):2487-94 |
| abstractText | 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. |
