Postnatal lethality in mice lacking the Sax2 homeobox gene homologous to Drosophila S59/slouch: evidence for positive and negative autoregulation.
Postnatal lethality in mice lacking the Sax2 homeobox gene homologous to Drosophila S59/slouch: evidence for positive and negative autoregulation.
复制标题
缺乏与果蝇 S59/slouch 同源的 Sax2 同源盒基因的小鼠的产后致死率：正向和负向自动调节的证据。
DOI：
10.1128/mcb.23.24.9046-9060.2003
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发表时间：
2003
影响因子：
5.3
通讯作者：
Lufkin,Thomas
中科院分区：
文献类型：
--
作者：
Simon,Ruth;Lufkin,Thomas
同源框基因转录因子在发育过程中指导多种功能。它们参与胚胎的早期模式以及细胞规格、细胞分化和器官发生。在这里，我们描述了一种以前未表征的鼠类同源盒基因 Sax2，它与果蝇 S59/slouch 和鼠类 Sax1 基因高度相似。我们发现Sax2基因表达发生在胚胎发生早期的中脑、中脑-后脑边界、腹侧神经管、发育中的眼睛和四肢的顶端外胚层脊。为了确定 Sax2 在发育过程中的作用，我们通过用 lacZ 基因替换部分 Sax2 编码序列来生成敲除小鼠品系。 Sax2null等位基因突变体表现出强烈的表型，表现为出生后立即开始生长迟缓，并导致出生后前3周内过早死亡。有趣的是，我们的研究还表明，根据表达 Sax2 的特定细胞类型，Sax2 基因在正反馈和负反馈机制中具有显着的自动调节作用。
Homeobox gene transcription factors direct multiple functions during development. They are involved in early patterning of the embryo as well as cell specification, cell differentiation, and organogenesis. Here we describe a previously uncharacterized murine homeobox gene,Sax2, that shows high similarity to theDrosophila S59/slouchand murineSax1genes. We show thatSax2gene expression occurs early during embryogenesis in the midbrain, the midbrain-hindbrain boundary, the ventral neural tube, the developing eye, and the apical ectodermal ridge of the limb. To determine the role ofSax2during development, we generated a knockout mouse line by replacing part of theSax2coding sequences with thelacZgene. TheSax2null allele mutants exhibit a strong phenotype indicated by growth retardation starting immediately after birth and leading to premature death within the first 3 weeks postnatal. Intriguingly, our studies also demonstrated a striking autoregulation of theSax2gene in both positive- and negative-feedback mechanisms depending on the specific cell type expressingSax2.