Myosin-X knockout is semi-lethal and demonstrates that myosin-X functions in neural tube closure, pigmentation, hyaloid vasculature regression, and filopodia formation.
Myosin-X knockout is semi-lethal and demonstrates that myosin-X functions in neural tube closure, pigmentation, hyaloid vasculature regression, and filopodia formation.
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DOI：
10.1038/s41598-017-17638-x
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发表时间：
2017-12-11
影响因子：
4.6
通讯作者：
Cheney RE
中科院分区：
文献类型：
--
作者：
Heimsath EG Jr;Yim YI;Mustapha M;Hammer JA;Cheney RE
肌球蛋白-X（Myo 10）是一种非传统的肌球蛋白，以其在丝状伪足尖端的显著定位而闻名。尽管Myo 10在脊椎动物组织中广泛表达，但其在生物体水平上的功能仍然很大程度上未知。我们在这里报告KO-第一代（Myo 10 tm 1a/tm 1a），floxed（Myo 10 tm 1c/tm 1c）和KO小鼠（Myo 10 tm 1d/tm 1d）。Myo 10的完全敲除是半致死性的，超过一半的纯合KO胚胎表现出露脑畸形，这是神经管闭合的严重缺陷。出生后存活的所有Myo 10 KO小鼠均表现出白色腹部斑点，所有小鼠的眼中均存在持续的胎儿血管系统，约50%的小鼠具有蹼状趾。出生后存活的Myo 10 KO小鼠可以繁殖并产生一窝KO胚胎，这表明Myo 10对有丝分裂、减数分裂、成年存活或生育力不是绝对必需的。KO-第一小鼠和独立的自发缺失（Myo 10 m1 J/m1 J）表现出相同的核心表型。在视网膜血管生成过程中，KO小鼠表现出内皮丝状伪足减少约50%，表明Myo 10是体内形成正常数量丝状伪足所必需的。这里产生的Myo 10小鼠证明了Myo 10在哺乳动物发育中具有重要功能，并为定义Myo 10在体内的功能提供了关键工具。
Myosin-X (Myo10) is an unconventional myosin best known for its striking localization to the tips of filopodia. Despite the broad expression of Myo10 in vertebrate tissues, its functions at the organismal level remain largely unknown. We report here the generation of KO-first (Myo10 tm1a/tm1a), floxed (Myo10 tm1c/tm1c), and KO mice (Myo10 tm1d/tm1d). Complete knockout of Myo10 is semi-lethal, with over half of homozygous KO embryos exhibiting exencephaly, a severe defect in neural tube closure. All Myo10 KO mice that survive birth exhibit a white belly spot, all have persistent fetal vasculature in the eye, and ~50% have webbed digits. Myo10 KO mice that survive birth can breed and produce litters of KO embryos, demonstrating that Myo10 is not absolutely essential for mitosis, meiosis, adult survival, or fertility. KO-first mice and an independent spontaneous deletion (Myo10 m1J/m1J) exhibit the same core phenotypes. During retinal angiogenesis, KO mice exhibit a ~50% decrease in endothelial filopodia, demonstrating that Myo10 is required to form normal numbers of filopodia in vivo. The Myo10 mice generated here demonstrate that Myo10 has important functions in mammalian development and provide key tools for defining the functions of Myo10 in vivo.
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影响因子：
11.4
作者：
Hirano, Yoshinori;Hatano, Taiki;Takahashi, Aya;Toriyama, Michinori;Inagaki, Naoyuki;Hakoshima, Toshio
通讯作者：
Hakoshima, Toshio
DOI：
10.1073/pnas.2334417100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Belyantseva, IA;Boger, ET;Friedman, TB
通讯作者：
Friedman, TB
影响因子：
16.8
作者：
Healey, Eleanor G.;Bishop, Benjamin;Elegheert, Jonathan;Bell, Christian H.;Padilla-Parra, Sergi;Siebold, Christian
通讯作者：
Siebold, Christian
影响因子：
64.8
作者：
Dickinson ME;Flenniken AM;Ji X;Teboul L;Wong MD;White JK;Meehan TF;Weninger WJ;Westerberg H;Adissu H;Baker CN;Bower L;Brown JM;Caddle LB;Chiani F;Clary D;Cleak J;Daly MJ;Denegre JM;Doe B;Dolan ME;Edie SM;Fuchs H;Gailus-Durner V;Galli A;Gambadoro A;Gallegos J;Guo S;Horner NR;Hsu CW;Johnson SJ;Kalaga S;Keith LC;Lanoue L;Lawson TN;Lek M;Mark M;Marschall S;Mason J;McElwee ML;Newbigging S;Nutter LM;Peterson KA;Ramirez-Solis R;Rowland DJ;Ryder E;Samocha KE;Seavitt JR;Selloum M;Szoke-Kovacs Z;Tamura M;Trainor AG;Tudose I;Wakana S;Warren J;Wendling O;West DB;Wong L;Yoshiki A;International Mouse Phenotyping Consortium;Jackson Laboratory;Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS);Charles River Laboratories;MRC Harwell;Toronto Centre for Phenogenomics;Wellcome Trust Sanger Institute;RIKEN BioResource Center;MacArthur DG;Tocchini-Valentini GP;Gao X;Flicek P;Bradley A;Skarnes WC;Justice MJ;Parkinson HE;Moore M;Wells S;Braun RE;Svenson KL;de Angelis MH;Herault Y;Mohun T;Mallon AM;Henkelman RM;Brown SD;Adams DJ;Lloyd KC;McKerlie C;Beaudet AL;Bućan M;Murray SA
通讯作者：
Murray SA
影响因子：
21.3
作者：
Berg, JS;Cheney, RE
通讯作者：
Cheney, RE