Loss of lysyl oxidase-like 3 causes cleft palate and spinal deformity in mice.
Loss of lysyl oxidase-like 3 causes cleft palate and spinal deformity in mice.
复制标题
赖氨酰氧化酶样 3 的缺失导致小鼠腭裂和脊柱畸形
DOI：
10.1093/hmg/ddv333
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发表时间：
2015-11-01
影响因子：
3.5
通讯作者：
Gao J
中科院分区：
文献类型：
--
作者：
Zhang J;Yang R;Liu Z;Hou C;Zong W;Zhang A;Sun X;Gao J
在哺乳动物中，胚胎发育是受遗传因素严格控制的高度调节的形态发生过程。这些过程中的任何一个失败都可能导致胚胎畸形。赖氨酰氧化酶（LOX）家族基因与人类疾病密切相关。在这项研究中，我们研究了赖氨酰氧化酶样3（LOXL3），LOX家族的成员，在胚胎发育中的重要作用。缺乏LOXL3的小鼠表现出围产期致死性，并且Loxl3基因的缺失导致腭架发育受损、胸椎软骨原基异常和轻度牙槽萎缩。我们发现，由于LOXL3的缺失，导致腭和脊柱中胶原交联的明显减少，从而导致腭裂和脊柱畸形。因此，我们提供了关键的体内证据，LOXL3是小鼠腭发育和脊柱发育不可或缺的。Loxl3基因可能是导致腭裂和脊柱畸形的候选疾病基因。
In mammals, embryonic development are highly regulated morphogenetic processes that are tightly controlled by genetic elements. Failure of any one of these processes can result in embryonic malformation. The lysyl oxidase (LOX) family genes are closely related to human diseases. In this study, we investigated the essential role of lysyl oxidase-like 3 (LOXL3), a member of the LOX family, in embryonic development. Mice lacking LOXL3 exhibited perinatal lethality, and the deletion of the Loxl3 gene led to impaired development of the palate shelves, abnormalities in the cartilage primordia of the thoracic vertebrae and mild alveolar shrinkage. We found that the obvious decrease of collagen cross-links in palate and spine that was induced by the lack of LOXL3 resulted in cleft palate and spinal deformity. Thus, we provide critical in vivo evidence that LOXL3 is indispensable for mouse palatogenesis and vertebral column development. The Loxl3 gene may be a candidate disease gene resulting in cleft palate and spinal deformity.