A Naturally Fluorescent Mgp Transgenic Mouse for Angiogenesis and Glaucoma Longitudinal Studies.
A Naturally Fluorescent Mgp Transgenic Mouse for Angiogenesis and Glaucoma Longitudinal Studies.
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DOI：
10.1167/iovs.17-22992
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发表时间：
2018-02-01
影响因子：
4.4
通讯作者：
Borrás T
中科院分区：
文献类型：
--
作者：
Asokan P;Mitra RN;Periasamy R;Han Z;Borrás T
我们的目标是产生和表征一种新的小鼠模型，其中只有血管生成和肿瘤相关组织会自然发荧光。基质Gla（MGP）基因在血管平滑肌细胞（VSMC）和小梁网（TM）中高度表达。我们试图将我们的Mgp-Cre.KI小鼠重组酶导向VSMC/TM细胞以产生它们的纵向荧光谱。将纯合Mgp-Cre.KI小鼠与Ai 9纯合报告小鼠杂交，所述Ai 9纯合报告小鼠具有防止DsRed荧光蛋白转录的loxP侧翼STOP盒（tdTomato）。通过直接荧光、整体封片、组织学和眼底照相检查F1双杂合子（Mgp-tdTomato）。定制的过滤器具有554/23发射和609/54激发纳米波长。通过诱导引导成像激光烧伤来进行模型有用性的概念证明。评估血管的泄漏和增殖，其次是无创血管造影。Mgp-tdTomato小鼠存活，可生育，IOP和ERG正常。它的表型表现为红色的爪子和鼻子（软骨表达），这排除了基因分型。在利姆布斯处观察到荧光红色环，并通过组织学证实为TM表达。整个视网膜血管是红色荧光（VSMC），并直接可视化眼底照相。Mgp-tdTomato上的激光灼伤允许分离渗漏和新血管形成评价参数。转基因小鼠在青光眼相关组织和视网膜血管系统中天然荧光的可用性为在体内研究广谱的单一和组合的青光眼病症带来了独特的机会。此外，Mgp-tdTomato小鼠为纵向研究视网膜血管生成机制和治疗提供了新的工具。
Our goal was to generate and characterize a new mouse model in which only angiogenesis- and glaucoma-relevant tissues would be naturally fluorescent. The Matrix Gla (MGP) gene is highly expressed in vascular smooth muscle cells (VSMC) and trabecular meshwork (TM). We sought to direct our Mgp-Cre.KI mouse recombinase to VSMC/TM cells to produce their longitudinal fluorescent profiles. Homozygous Mgp-Cre.KI mice were crossed with Ai9 homozygous reporter mice harboring a loxP-flanked STOP cassette preventing transcription of a DsRed fluorescent protein (tdTomato). The F1 double-heterozygous (Mgp-tdTomato) was examined by direct fluorescence, whole mount, histology, and fundus photography. Custom-made filters had 554/23 emission and 609/54 exciter nanometer wavelengths. Proof of concept of the model's usefulness was conducted by inducing guided imaging laser burns. Evaluation of a vessel's leakage and proliferation was followed by noninvasive angiography. The Mgp-tdTomato mouse was viable, fertile, with normal IOP and ERG. Its phenotype exhibited red paws and snout (cartilage expression), which precluded genotyping. A fluorescent red ring was seen at the limbus and confirmed to be TM expression by histology. The entire retinal vasculature was red fluorescent (VSMC) and directly visualized by fundus photography. Laser burns on the Mgp-tdTomato allowed separation of leakiness and neovascularization evaluation parameters. The availability of a transgenic mouse naturally fluorescent in glaucoma-relevant tissues and retinal vasculature brings the unique opportunity to study a wide spectrum of single and combined glaucomatous conditions in vivo. Moreover, the Mgp-tdTomato mouse provides a new tool to study mechanisms and therapeutics of retinal angiogenesis longitudinally.
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影响因子：
4.6
作者：
Matsushita J;Inagaki S;Nishie T;Sakasai T;Tanaka J;Watanabe C;Mizutani KI;Miwa Y;Matsumoto K;Takara K;Naito H;Kidoya H;Takakura N;Nagai T;Takahashi S;Ema M
通讯作者：
Ema M
影响因子：
4.8
作者：
Iljin, K;Petrova, TV;Alitalo, K
通讯作者：
Alitalo, K
影响因子：
3.4
作者：
Lu, Zhaozeng;Overby, Darryl R.;Gong, Haiyan
通讯作者：
Gong, Haiyan
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
影响因子：
7.4
作者：
Mitra, Rajendra N.;Merwin, Miles J.;Han, Zongchao;Conley, Shannon M.;Al-Ubaidi, Muayyad R.;Naash, Muna I.
通讯作者：
Naash, Muna I.