University Program in Genetics and Genomics, Duke University Graduate School, Durham, North Carolina, USA.
Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA.
Genesis. 2024 Aug;62(4):e23615. doi: 10.1002/dvg.23615.
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 Armcx1 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 Armcx1 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.
Armcx1 蛋白是一种跨膜蛋白,其包含多个 Armadillo 重复序列,但目前其功能仍不清楚。该蛋白在神经元中能够调控线粒体的运输,其过表达能够诱导胚胎神经元的轴突生长,并能促进视神经挤压模型中小鼠视网膜神经节细胞(RGC)的存活和轴突再生。为了研究 Armcx1 蛋白在体内的功能,我们构建了条件性 Armcx1 基因敲除小鼠,该小鼠的 Armcx1 基因编码区被loxP 位点所包围。利用 Armcx1 条件性敲除小鼠分别与表达 Cre 重组酶的β-actin 和 Six3 启动子小鼠杂交,实现了 Armcx1 基因在小鼠体内的敲除。通过基因敲除确认后,我们进一步研究了 15 月龄的 Armcx1 基因敲除小鼠中 RGC 的数量和形态。在正常生理条件下,这些小鼠的视网膜或视神经发育以及 RGC 变性均无异常。该 Armcx1 基因敲除小鼠将有助于进一步研究 Armcx1 缺失对线粒体形态和运输的影响,以及确定 Armcx1 缺失神经元在其它遗传或环境应激因素下易变性的机制。