Generation and Characterization of a Novel Mouse Model That Allows Spatiotemporal Quantification of Pancreatic β-Cell Proliferation.
Generation and Characterization of a Novel Mouse Model That Allows Spatiotemporal Quantification of Pancreatic β-Cell Proliferation.
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作者：
Tokumoto S;Yabe D;Tatsuoka H;Usui R;Fauzi M;Botagarova A;Goto H;Herrera PL;Ogura M;Inagaki N
胰腺β-细胞增殖作为预防和治疗糖尿病的治疗靶点已受到广泛关注。为了评价潜在的β细胞有丝分裂原，用于检测和定量β细胞增殖率的准确和可靠的方法是必不可少的。在这项研究中，我们开发了一种新的工具，通过使用在β细胞中表达基于荧光泛素化的细胞周期指示剂Fucci 2a的RIP-Cre; R26 Fucci 2aR小鼠，将复制的β细胞特异性标记为mVenus+细胞。在对β细胞增殖刺激（如胰岛素受体拮抗剂S961和饮食诱导的肥胖症（DIO））的反应中，这些小鼠中每个胰岛素+细胞的5-乙炔基-2 ′-脱氧尿苷阳性胰岛素+细胞数量和每个mCherry+ mVenus−细胞+ mCherry− mVenus+细胞的mVenus+细胞数量相似地增加。来自这些小鼠的光学透明的胰腺组织的三维成像使得能够量化胰岛中的复制β细胞和已知促有丝分裂干预（例如S961、DIO、妊娠和部分胰腺切除术）后的胰岛的形态测定分析。因此，这种新型小鼠系是用于时空分析和定量响应于促有丝分裂刺激的β细胞增殖的有力工具。
Pancreatic β-cell proliferation has been gaining much attention as a therapeutic target for the prevention and treatment of diabetes. In order to evaluate potential β-cell mitogens, accurate and reliable methods for the detection and quantification of the β-cell proliferation rate are indispensable. In this study, we developed a novel tool that specifically labels replicating β-cells as mVenus+ cells by using RIP-Cre; R26Fucci2aR mice expressing the fluorescent ubiquitination-based cell cycle indicator Fucci2a in β-cells. In response to β-cell proliferation stimuli, such as insulin receptor antagonist S961 and diet-induced obesity (DIO), the number of 5-ethynyl-2′-deoxyuridine-positive insulin+ cells per insulin+ cells and the number of mVenus+ cells per mCherry+ mVenus− cells + mCherry− mVenus+ cells were similarly increased in these mice. Three-dimensional imaging of optically cleared pancreas tissue from these mice enabled quantification of replicating β-cells in the islets and morphometric analysis of the islets after known mitogenic interventions such as S961, DIO, pregnancy, and partial pancreatectomy. Thus, this novel mouse line is a powerful tool for spatiotemporal analysis and quantification of β-cell proliferation in response to mitogenic stimulation.
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影响因子：
29
作者：
Porat, Shay;Weinberg-Corem, Noa;Dor, Yuval
通讯作者：
Dor, Yuval
影响因子：
64.5
作者：
Sakaue-Sawano, Asako;Kurokawa, Hiroshi;Miyawaki, Atsushi
通讯作者：
Miyawaki, Atsushi
影响因子：
7.7
作者：
Jiao Y;Le Lay J;Yu M;Naji A;Kaestner KH
通讯作者：
Kaestner KH
影响因子：
3.7
作者：
Cox AR;Barrandon O;Cai EP;Rios JS;Chavez J;Bonnyman CW;Lam CJ;Yi P;Melton DA;Kushner JA
通讯作者：
Kushner JA
影响因子：
4.1
作者：
Herrera, PL;Orci, L;Vassalli, JD
通讯作者：
Vassalli, JD