...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Dyrk1A Haploinsufficiency Affects Viability and Causes Developmental Delay and Abnormal Brain Morphology in Mice
【24h】

Dyrk1A Haploinsufficiency Affects Viability and Causes Developmental Delay and Abnormal Brain Morphology in Mice

机译：Dyrk1A单倍型不足影响小鼠的生存能力，并导致发育延迟和脑形态异常。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is involved in postembryonic neurogenesis in flies. Because of its mapping position on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing this gene, involvement of DYRK1A in some of the neurological defects of Down syndrome patients has been suggested. To gain insight into its physiological role, we have generated mice deficient in Dyrk1A function by gene targeting. Dyrk1A?/? null mutants presented a general growth delay and died during midgestation. Mice heterozygous for the mutation (Dyrk1A+/?) showed decreased neonatal viability and a significant body size reduction from birth to adulthood. General neurobehavioral analysis revealed preweaning developmental delay of Dyrk1A+/? mice and specific alterations in adults. Brains of Dyrk1A+/? mice were decreased in size in a region-specific manner, although the cytoarchitecture and neuronal components in most areas were not altered. Cell counts showed increased neuronal densities in some brain regions and a specific decrease in the number of neurons in the superior colliculus, which exhibited a significant size reduction. These data provide evidence about the nonredundant, vital role of Dyrk1A and suggest a conserved mode of action that determines normal growth and brain size in both mice and flies.
机译： DYRK1A 是果蝇小脑蝇（ mnb ）基因的人类直系同源基因，它与果蝇的胚胎后神经发生有关。由于它在21号染色体上的作图位置以及过表达该基因的小鼠表现出的神经行为改变，提示DYRK1A参与了唐氏综合症患者的某些神经系统缺陷。为了深入了解其生理作用，我们已经通过基因定位产生了缺乏Dyrk1A功能的小鼠。 Dyrk1A ？/？空突变体表现出普遍的生长延迟，并在妊娠中期死亡。杂合子突变的小鼠（Dyrk1A + /？）显示出新生儿的生存能力下降，并且从出生到成年都显着减小了体型。常规神经行为学分析显示Dyrk1A + /？小鼠断奶前发育延迟和成年小鼠的特定改变。 Dyrk1A + /？小鼠的大脑大小以区域特异性方式减小，尽管大多数区域的细胞结构和神经元成分均未改变。细胞计数显示某些大脑区域的神经元密度增加，而上丘中神经元的数量则明显减少，这表明大小明显减少。这些数据提供了关于 Dyrk1A 的非冗余，至关重要的作用的证据，并提出了一种保守的作用方式，该作用方式决定了小鼠和果蝇的正常生长和大脑大小。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号