Lange Alexander W, Rothermel Beverly A, Yutzey Katherine E
Division of Molecular Cardiovascular Biology, Children's Medical Center Cincinnati, Cincinnati, Ohio 45229, USA.
Dev Dyn. 2005 Jul;233(3):954-63. doi: 10.1002/dvdy.20433.
The Down syndrome critical region 1 (DSCR1) gene is located in syntenic regions of human chromosome 21 and mouse chromosome 16 and encodes a regulatory protein in the calcineurin/NFAT pathway. DSCR1 expression in the embryonic brain, craniofacial structures, and heart is consistent with a role in contributing to Down syndrome developmental anomalies. In the trisomy 16 (Ts16) murine model of Down syndrome, expression of DSCR1 isoforms is elevated and NFAT transcriptional activity is decreased in the developing heart and brain. The individual contribution of DSCR1 to Down syndrome-related anomalies was examined by specific restoration of DSCR1 to disomic levels in Ts16 embryos. However, genetic restoration of DSCR1 did not rescue major morphological abnormalities in cardiac or craniofacial development. These data demonstrate that trisomy of DSCR1 alone does not significantly contribute to developmental defects in Ts16 mice and underscore the complexity of developmental anomalies associated with Down syndrome.
唐氏综合征关键区域1（DSCR1）基因位于人类21号染色体和小鼠16号染色体的同线区域，在钙调神经磷酸酶/NFAT信号通路中编码一种调节蛋白。DSCR1在胚胎脑、颅面结构和心脏中的表达与唐氏综合征发育异常的发生机制相符。在唐氏综合征的16三体（Ts16）小鼠模型中，发育中的心脏和大脑中DSCR1亚型的表达升高，NFAT转录活性降低。通过将DSCR1特异性恢复到Ts16胚胎的二体水平，研究了DSCR1对唐氏综合征相关异常的个体影响。然而，DSCR1的基因恢复并未挽救心脏或颅面发育中的主要形态异常。这些数据表明，单独的DSCR1三体并不显著导致Ts16小鼠的发育缺陷，并强调了与唐氏综合征相关的发育异常的复杂性。
