Armcx1 条件性基因敲除小鼠的产生

IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis Pub Date : 2024-08-14 DOI:10.1002/dvg.23615
Cora L. Bright, Howard M. Bomze, Mantu Bhaumik, Jeremy N. Kay, Romain Cartoni, Sidney M. Gospe III
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引用次数: 0

摘要

含犰狳重复的 X 连锁蛋白-1(Armcx1)是一种特征不明显的跨膜蛋白,可调节神经元中线粒体的转运。研究表明,过表达Armcx1可诱导胚胎神经元的神经元突起,并在小鼠视神经挤压模型中促进视网膜神经节细胞(RGC)的存活和轴突再生。为了评估内源性Armcx1在体内的功能,我们创建了一个条件性Armcx1基因敲除小鼠品系,在该品系中,Armcx1基因的整个编码区都被loxP位点包绕。将这一Armcx1fl品系与Cre重组酶的表达由β-肌动蛋白和Six3启动子驱动的小鼠品系杂交,以分别实现Armcx1基因在全球和视网膜神经元中的缺失。在确认基因缺失后,我们开始研究年龄为15个月的Armcx1基因敲除小鼠的RGC数量和形态特征。在正常生理条件下,这些小鼠没有观察到视网膜或视神经发育异常或 RGC 退化的迹象。Armcx1fl小鼠对于未来研究Armcx1缺失时线粒体形态和转运,以及确定Armcx1缺失神经元在额外遗传或环境压力下的变性易感性都很有价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Generation of an Armcx1 Conditional Knockout Mouse

Armadillo repeat-containing X-linked protein-1 (Armcx1) is a poorly characterized transmembrane protein that regulates mitochondrial transport in neurons. Its overexpression has been shown to induce neurite outgrowth in embryonic neurons and to promote retinal ganglion cell (RGC) survival and axonal regrowth in a mouse optic nerve crush model. In order to evaluate the functions of endogenous Armcx1 in vivo, we have created a conditional Armcx1 knockout mouse line in which the entire coding region of the Armcx1 gene is flanked by loxP sites. This Armcx1fl line was crossed with mouse strains in which Cre recombinase expression is driven by the promoters for β-actin and Six3, in order to achieve deletion of Armcx1 globally and in retinal neurons, respectively. Having confirmed deletion of the gene, we proceeded to characterize the abundance and morphology of RGCs in Armcx1 knockout mice aged to 15 months. Under normal physiological conditions, no evidence of aberrant retinal or optic nerve development or RGC degeneration was observed in these mice. The Armcx1fl mouse should be valuable for future studies investigating mitochondrial morphology and transport in the absence of Armcx1 and in determining the susceptibility of Armcx1-deficient neurons to degeneration in the setting of additional heritable or environmental stressors.

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来源期刊
genesis
genesis 生物-发育生物学
CiteScore
3.60
自引率
0.00%
发文量
40
审稿时长
6-12 weeks
期刊介绍: As of January 2000, Developmental Genetics was renamed and relaunched as genesis: The Journal of Genetics and Development, with a new scope and Editorial Board. The journal focuses on work that addresses the genetics of development and the fundamental mechanisms of embryological processes in animals and plants. With increased awareness of the interplay between genetics and evolutionary change, particularly during developmental processes, we encourage submission of manuscripts from all ecological niches. The expanded numbers of genomes for which sequencing is being completed will facilitate genetic and genomic examination of developmental issues, even if the model system does not fit the “classical genetic” mold. Therefore, we encourage submission of manuscripts from all species. Other areas of particular interest include: 1) the roles of epigenetics, microRNAs and environment on developmental processes; 2) genome-wide studies; 3) novel imaging techniques for the study of gene expression and cellular function; 4) comparative genetics and genomics and 5) animal models of human genetic and developmental disorders. genesis presents reviews, full research articles, short research letters, and state-of-the-art technology reports that promote an understanding of the function of genes and the roles they play in complex developmental processes.
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