鸟氨酸-δ-氨基转移酶在非洲爪蟾胚胎发育过程中抑制神经发生。

Ornithine-δ-Aminotransferase Inhibits Neurogenesis During Xenopus Embryonic Development.

作者信息

Peng Ying, Cooper Sandra K, Li Yi, Mei Jay M, Qiu Shuwei, Borchert Gregory L, Donald Steven P, Kung Hsiang-Fu, Phang James M

机构信息

Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Basic Research Program, Leidos, Inc., National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, United States.

出版信息

Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2486-97. doi: 10.1167/iovs.15-16509.

DOI:10.1167/iovs.15-16509

PMID:25783604

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4554259/

Abstract

PURPOSE

In humans, deficiency of ornithine-δ-aminotransferase (OAT) results in progressive degeneration of the neural retina (gyrate atrophy) with blindness in the fourth decade. In this study, we used the Xenopus embryonic developmental model to study functions of the OAT gene on embryonic development.

METHODS

We cloned and sequenced full-length OAT cDNA from Xenopus oocytes (X-OAT) and determined X-OAT expression in various developmental stages of Xenopus embryos and in a variety of adult tissues. The phenotype, gene expression of neural developmental markers, and enzymatic activity were detected by gain-of-function and loss-of-function manipulations.

RESULTS

We showed that X-OAT is essential for Xenopus embryonic development, and overexpression of X-OAT produces a ventralized phenotype characterized by a small head, lack of axial structure, and defective expression of neural developmental markers. Using X-OAT mutants based on mutations identified in humans, we found that substitution of both Arg 180 and Leu 402 abrogated both X-OAT enzymatic activity and ability to modulate the developmental phenotype. Neurogenesis is inhibited by X-OAT during Xenopus embryonic development.

CONCLUSIONS

Neurogenesis is inhibited by X-OAT during Xenopus embryonic development, but it is essential for Xenopus embryonic development. The Arg 180 and Leu 402 are crucial for these effects of the OAT molecule in development.

摘要

目的

在人类中，鸟氨酸 - δ - 氨基转移酶（OAT）缺乏会导致神经视网膜进行性退化（回旋状萎缩），并在四十岁左右失明。在本研究中，我们使用非洲爪蟾胚胎发育模型来研究OAT基因在胚胎发育中的功能。

方法

我们从非洲爪蟾卵母细胞中克隆并测序了全长OAT cDNA（X - OAT），并确定了X - OAT在非洲爪蟾胚胎不同发育阶段以及多种成体组织中的表达情况。通过功能获得和功能丧失操作检测了表型、神经发育标志物的基因表达以及酶活性。

结果

我们发现X - OAT对非洲爪蟾胚胎发育至关重要，X - OAT的过表达会产生一种腹化表型，其特征为头部小、缺乏轴向结构以及神经发育标志物表达缺陷。利用基于在人类中鉴定出的突变构建的X - OAT突变体，我们发现Arg 180和Leu 402的替换同时消除了X - OAT的酶活性和调节发育表型的能力。在非洲爪蟾胚胎发育过程中，神经发生受到X - OAT的抑制。