SMOC1 Is Essential for Ocular and Limb Development in Humans and Mice
SMOC1 Is Essential for Ocular and Limb Development in Humans and Mice
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DOI：
10.1016/j.ajhg.2010.11.012
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发表时间：
2011-01-07
影响因子：
9.8
通讯作者：
Saitsu, Hirotomo
中科院分区：
文献类型：
--
作者：
Okada, Ippei;Hamanoue, Haruka;Saitsu, Hirotomo
小眼畸形伴肢体畸形是一种罕见的常染色体隐性遗传疾病，临床表现为无眼或小眼以及手和/或足畸形。我们将MLA基因定位于14 q24，并在三个家族中成功地鉴定出了三个纯合突变（一个无义突变和两个剪接位点），这些突变发生在与酸性和富含半胱氨酸的分泌蛋白相关的模块化钙结合1（SMOC 1）中。Smoc 1在小鼠胚胎发育中的视柄、腹侧视杯和四肢中表达。Smoc 1基因敲除小鼠再现了MLA表型，包括视神经发育不全或发育不全、腓骨发育不全和胫骨弯曲以及四肢并指。还观察到变薄和不规则的神经节细胞层和视网膜前腹侧部分萎缩。软组织并指畸形，由于抑制细胞凋亡，涉及BMP信号在指间间充质中的基因表达紊乱。我们的研究结果表明，SMOC 1/Smoc 1对人类和小鼠的眼睛和肢体发育至关重要。
Microphthalmia with limb anomalies (MLA) is a rare autosomal-recessive disorder, presenting with anophthalmia or microphthalmia and hand and/or foot malformation. We mapped the MLA locus to 14q24 and successfully identified three homozygous (one nonsense and two splice site) mutations in the SPARC (secreted protein acidic and rich in cysteine)-related modular calcium binding 1 (SMOC1) in three families. Smoc1 is expressed in the developing optic stalk, ventral optic cup, and limbs of mouse embryos. Smoc1 null mice recapitulated MLA phenotypes, including aplasia or hypoplasia of optic nerves, hypoplastic fibula and bowed tibia, and syndactyly in limbs. A thinned and irregular ganglion cell layer and atrophy of the anteroventral part of the retina were also observed. Soft tissue syndactyly, resulting from inhibited apoptosis, was related to disturbed expression of genes involved in BMP signaling in the interdigital mesenchyme. Our findings indicate that SMOC1/Smoc1 is essential for ocular and limb development in both humans and mice.