Microform holoprosencephaly in mice that lack the Ig superfamily member Cdon
Microform holoprosencephaly in mice that lack the Ig superfamily member Cdon
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DOI：
10.1016/s0960-9822(03)00088-5
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发表时间：
2003-03-04
期刊：
影响因子：
9.2
通讯作者：
Krauss, RS
中科院分区：
文献类型：
--
作者：
Cole, F;Krauss, RS
前脑无裂畸形（HPE）是前脑和面中部最常见的发育缺陷，是由于未能在这些结构中描绘中线而引起的[1，2]。尽管已经鉴定出几个HPE基因，但其遗传基础在很大程度上是未知的。此外，受影响个体的表型是高度可变的，即使在家系内[3，4]。HPE的面部缺陷范围从严重病例中的独眼和长鼻到患有HPE的个体中的孤立的上颌正中中切牙。Cdon（也称为Cdo）是IG超家族成员，是正调节骨骼肌发生的细胞表面受体的组分[5-7]。Cdon还在发育中的小鼠胚胎的额鼻突和上颌骨突（分别为FNP和MXP）中高度表达[8]：含有图案化面部的信号传导中心的结构[9，10]。我们在此报告，Cdon靶向突变纯合子小鼠显示与HPE微形态相关的标志性面部缺陷。这是具有这种表型的小鼠突变体的第一个例子，这一发现暗示了面部中线发育中的一个新的受体家族，并表明Cdon在人类HPE的发病机制和表达中的潜在作用。
Holoprosencephaly (HPE), the most common developmental defect of the forebrain and midface, is caused by a failure to delineate the midline in these structures [1, 2]. Despite the identification of several HPE genes, its genetic basis is largely unknown. Furthermore, the phenotype of affected individuals is highly variable, even within pedigrees [3, 4]. Facial defects in HPE range from cyclopia and proboscis in severe cases to solitary median maxillary central incisor in individuals with microforms of HPE. Cdon (also known as Cdo), an Ig superfamily member, is a component of a cell surface receptor that positively regulates skeletal myogenesis [5-7]. Cdon is also highly expressed in the frontonasal and maxillary processes (FNP and MXP respectively) of the developing mouse embryo [8]: structures that contain signaling centers that pattern the face [9, 10]. We report here that mice homozygous for targeted mutations of Cdon display the hallmark facial defects associated with microforms of HPE. This is the first example of a mouse mutant with this phenotype, and this finding implicates a new family of receptors in development of the facial midline and suggests a potential role for Cdon in the pathogenesis and expressivity of HPE in humans.