| First Author | Koss M | Year | 2012 |
| Journal | Dev Cell | Volume | 22 |
| Issue | 5 | Pages | 913-26 |
| PubMed ID | 22560297 | Mgi Jnum | J:184521 |
| Mgi Id | MGI:5424277 | Doi | 10.1016/j.devcel.2012.02.009 |
| Citation | Koss M, et al. (2012) Congenital Asplenia in Mice and Humans with Mutations in a Pbx/Nkx2-5/p15 Module. Dev Cell 22(5):913-26 |
| abstractText | The molecular determinants of spleen organogenesis and the etiology of isolated congenital asplenia (ICA), a life-threatening human condition, are unknown. We previously reported that Pbx1 deficiency causes organ growth defects including asplenia. Here, we show that mice with splenic mesenchyme-specific Pbx1 inactivation exhibit hyposplenia. Moreover, the loss of Pbx causes downregulation of Nkx2-5 and derepression of p15Ink4b in spleen mesenchymal progenitors, perturbing the cell cycle. Removal of p15Ink4b in Pbx1 spleen-specific mutants partially rescues spleen growth. By whole-exome sequencing of a multiplex kindred with ICA, we identify a heterozygous missense mutation (P236H) in NKX2-5 showing reduced transactivation in vitro. This study establishes that a Pbx/Nkx2-5/p15 regulatory module is essential for spleen development. |
