Congenital asplenia in mice and humans with mutations in a Pbx/Nkx2-5/p15 module.
[No authors listed]
摘要
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.
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基因功能
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基因
Ly76, E2f4, Mtbp, Psmg2, Ltbp4, Bmp3, Amhr2, Abl1, Macf1, Acvr1, Acvr2a, Acvrl1, Ak1, Amh, Apbb1, Atm, Bglap2, Bmp1, Bmp2, Bmp4, Bmp5, Bmp6, Bmp7, Gdf2, Bmpr1a, Bmpr1b, Bmpr2, Brca1, Brca2, Camk2a, Camk2b, Casp3, Runx1, Ccna1, Ccna2, Ccnb2, Ccnd1, Ccne1, Ccnf, Cd79a, Cdc25a, Cdk2, Cdk4, Cdkn1a, Cdkn1b, Cdkn2a, Cdkn2b, Chek1, Chrd, Col3a1, Col1a1, Col1a2, Gadd45a, Ddit3, Dlx2, Dst, E2f1, E2f3, Lefty1, Eng, Mecom, Fkbp1b, Fos, Gdf1, Gdf3, Gdf5, Gsc, Gt(ROSA)26Sor, Hus1, Id1, Id2, Igf1, Igfbp3, Il6, Inha, Inhba, Inhbb, Itgb1, Itgb5, Itgb7, Jun, Junb, Ltbp2, Smad1, Smad2, Smad3, Smad4, Smad5, Mcm3, Mcm2, Mcm4, Mdm2, Mki67, Mre11a, Msh2, Myb, Myc, Nbl1, Nek2, Nfatc1, Nkx2-5, Nodal, Nog, Notch2, Pbx1, Pbx2, Pcna, Pdgfb, Pecam1, Pkd1, Serpine1, Plat, Plau, Pmp22, Ppp2r3d, Ppp3ca, Prm1, Rad17, Rad21, Rad51, Rad9a, Ran, Rbl1, Rbl2, Shc1, Slfn1, Sox4, Stag1, Stat1, Tdgf1, Terf1, Tfdp1, Tgfb1, Tgfb1i1, Tsc22d1, Tgfb2, Tgfb3, Tgfbi, Tgfbr1, Tgfbr2, Tgfbr3, Tlx1, Trp53, Trp63, Tsg101, Sumo1, Vim, Wee1, Dnajc2, Sesn2, Ppp2r3a, Gdf7, Smc1a, Taf10, Gdf6, E2f2, Ccnb1, Ltbp1, Skp2, Npm2, Ccnc, Ppm1d, Cks1b, Sfn, Mad2l1, Gpr132, Pes1, Cdk5rap1, Bambi, Tgfbrap1, Bmper, Smurf1, NKX2-5
原始数据
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文献解读
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