A defect in the mitochondrial protein Mpv17 underlies the transparent casper zebrafish.
A defect in the mitochondrial protein Mpv17 underlies the transparent casper zebrafish.
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DOI：
10.1016/j.ydbio.2017.07.017
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发表时间：
2017-10-01
影响因子：
2.7
通讯作者：
White RM
中科院分区：
文献类型：
--
作者：
D'Agati G;Beltre R;Sessa A;Burger A;Zhou Y;Mosimann C;White RM
斑马鱼的casper品系被广泛用于从癌症到神经科学的研究。Casper提供了在整个成年期相对透明的优点，使得其特别适用于通过落射荧光、共焦和光片显微镜进行的体内成像。Casper是通过对两种先前描述的隐性色素突变体进行选择性育种而开发的：1）珍珠层，其具有Mitfa基因的失活突变，使得鱼缺乏色素化的黑色素细胞;和2）Roy Orbison，其是具有迄今未鉴定的遗传原因的突变体，其缺乏反射性虹膜细胞。为了澄清罗伊奥比森突变的分子本质，以便它可以为使用casper的研究提供信息，我们进行了定位克隆罗伊奥比森突变的努力。我们发现roy orbison是由mpv 17基因的内含子缺陷引起的，mpv 17编码一种线粒体内膜蛋白，这种蛋白与人类线粒体DNA缺失综合征有关。罗伊奥比森突变是表型和分子显着相似的另一个斑马鱼虹膜突变称为透明。使用Cas9诱导的卷曲体和具有破坏的mpv 17开放阅读框的种系突变体，我们在反式杂合子胚胎中显示mpv 17、roy orbison和transparent的新移码等位基因不能彼此互补。我们的工作提供了遗传学证据，表明罗伊奥比森和透明通过相似的遗传损伤影响mpv 17位点。mpv 17突变体的鉴定将允许进一步的工作探索线粒体功能和色素沉着之间的关系，迄今为止很少受到关注。
The casper strain of zebrafish is widely used in studies ranging from cancer to neuroscience. casper offers the advantage of relative transparency throughout adulthood, making it particularly useful for in vivo imaging by epifluorescence, confocal, and light sheet microscopy. casper was developed by selective breeding of two previously described recessive pigment mutants: 1) nacre, which harbors an inactivating mutation of the mitfa gene, rendering the fish devoid of pigmented melanocytes; and 2) roy orbison, a mutant with so-far unidentified genetic cause that lacks reflective iridophores. To clarify the molecular nature of the roy orbison mutation, such that it can inform studies using casper, we undertook an effort to positionally clone the roy orbison mutation. We find that roy orbison is caused by an intronic defect in the gene mpv17, encoding an inner mitochondrial membrane protein that has been implicated in human mitochondrial DNA depletion syndrome. The roy orbison mutation is phenotypically and molecularly remarkably similar to another zebrafish iridophore mutant called transparent. Using Cas9-induced crispants and germline mutants with disrupted mpv17 open reading frame, we show in trans-heterozygote embryos that new frameshift alleles of mpv17, roy orbison, and transparent fail to complement each other. Our work provides genetic evidence that both roy orbison and transparent affect the mpv17 locus by a similar if not identical genetic lesion. Identification of mpv17 mutants will allow for further work probing the relationship between mitochondrial function and pigmentation, which has to date received little attention.
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影响因子：
3.7
作者：
Freeman, Jennifer L.;Ceol, Craig;Feng, Hui;Langenau, David M.;Belair, Cassandra;Stern, Howard M.;Song, Anhua;Paw, Barry H.;Look, A. Thomas;Zhou, Yi;Zon, Leonard I.;Lee, Charles
通讯作者：
Lee, Charles
影响因子：
4.5
作者：
Chen EY;Dobrinski KP;Brown KH;Clagg R;Edelman E;Ignatius MS;Chen JY;Brockmann J;Nielsen GP;Ramaswamy S;Keller C;Lee C;Langenau DM
通讯作者：
Langenau DM
影响因子：
3.5
作者：
Viscomi C;Spinazzola A;Maggioni M;Fernandez-Vizarra E;Massa V;Pagano C;Vettor R;Mora M;Zeviani M
通讯作者：
Zeviani M
影响因子：
2.7
作者：
Parichy, DM;Mellgren, EM;Johnson, SL
通讯作者：
Johnson, SL
影响因子：
4.6
作者：
Burger, Alexa;Lindsay, Helen;Mosimann, Christian
通讯作者：
Mosimann, Christian