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Neonatal Lethality, Dwarfism, and Abnormal Brain Development in Dmbx1 Mutant Mice

机译:Dmbx1突变小鼠的新生儿致死率,侏儒症和大脑发育异常。

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Dmbx1 encodes a paired-like homeodomain protein that is expressed in developing neural tissues during mouse embryogenesis. To elucidate the in vivo role of Dmbx1, we generated two Dmbx1 mutant alleles. Dmbx1? lacks the homeobox and Dmbx1z is an insertion of a lacZ reporter gene. Dmbx1z appears to be a faithful reporter of Dmbx1 expression during embryogenesis and after birth. Dmbx1-lacZ expression was detected in the superior colliculus, cerebellar nuclei, and subpopulations of the medulla oblongata and spinal cord. Some Dmbx1 homozygous mutant mice died during the neonatal period, while others survived to adulthood; however, their growth was impaired. Both heterozygous and homozygous mutant offspring from Dmbx1 homozygous mutant females exhibited a low survival rate and poor growth. However, even wild-type pups fostered onto Dmbx1 homozygous mutant females grew poorly, suggesting a Dmbx1-dependent nursing defect. Dmbx1 mutant mice had an aberrant Dmbx1-lacZ expression pattern in the nervous system, indicating that they had abnormal brain development. These results demonstrate that Dmbx1 is required for postnatal survival, growth, and brain development.
机译: Dmbx1 编码一种在小鼠胚胎发生过程中在发育中的神经组织中表达的成对同源结构域蛋白。为了阐明 Dmbx1 在体内的作用,我们产生了两个 Dmbx1 突变等位基因。 Dmbx1 ? 缺少同源框,而 Dmbx1 z lacZ 报告程序的插入基因。 Dmbx1 z 似乎是胚胎发生期间和出生后 Dmbx1 表达的忠实报道者。在上丘,小脑核以及延髓和脊髓亚群中检测到 Dmbx1-lacZ 表达。一些 Dmbx1 纯合突变小鼠在新生儿期死亡,而另一些存活到成年。但是,他们的成长受到了损害。 Dmbx1 纯合突变体雌性的杂合子和纯合突变体后代均显示出较低的成活率和较弱的生长。然而,即使是在 Dmbx1 纯合突变雌性上培育的野生幼崽生长也很差,表明 Dmbx1 依赖的护理缺陷。 Dmbx1 突变小鼠在神经系统中具有异常的 Dmbx1-lacZ 表达模式,表明它们的大脑发育异常。这些结果表明, Dmbx1 是出生后生存,生长和大脑发育所必需的。

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