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Animal models for brain arteriovenous malformation
S. Paul Oh 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7
Objective: Brain arteriovenous malformations (BAVMs) occur in about 10% of hereditary hemorrhagic telangiectasia (HHT) patients and can cause life-threating intracranial hemorrhage. Longitudinal studies that allow monitoring the birth and progression of BAVMs would be tremendous not only for understanding the natural history of BAVMs but also for developing preclinical models. Method: We used Tagln (SM22)-Cre:Alk1 <SUP>2f/2f</SUP> mice that were previously shown to develop BAVMs. GEFC (gradient echo with flow compensation) images were periodically acquired from the mutant and control mice starting at 1-2 months of age up to 14 months using Bruker 7T MR spectrometer. Tamoxifen inducible endothelial cell specific CreER (Scl -CreER) was used to determine critical stage of HHT gene deletion to cause BAVMs. Result: Brains of 55 Tagln -Cre (+);Alk1 <SUP>2f/2f</SUP> mutant mice studied with magnetic resonance angiography were categorized into three groups: no detectable vascular lesions (Group 1, 23 of 55, 42%); AV fistulas with no nidus (Group 2, 10 of 55, 18%); and nidal AVMs (Group 3, 22 of 55, 40%). AVMs had the angiographic hallmarks of early nidus opacification, a tangle of arteries and dilated draining veins, and rapid shunting of blood flow. Latex dye perfusion confirmed arteriovenous shunting in all AVMs and AV fistulas. Microhemorrhage was detected adjacent to AV fistulas and AVMs, as visualized by iron deposition, Prussian blue staining, and macrophage infiltration using CD68 immunostaining. Brain AVMs were largely stable over 12 months. Scl -CreER;Eng <SUP>2f/2f </SUP>mice develop BAVMs only when tamoxifen is treated before 2 weeks-old age, indicating a critical developmental timing for ALK1- or ENGdeficiency to cause BAVMs. Conclusion: This longitudinal study platform will be a great resource for studying risk factors for BAVM rupture and for evaluating potential drugs that may induce regression of BAVMs.
Oh, Young-Suk,Kenea, S. Takele,Goo, Tae-Young,Chung, Kyu-Sun,Rhee, Jae-Sang,Ou, Mi-Lim,Byun, Young-Hwa,Wennberg, Paul O.,Kiel, Matthä,us,DiGangi, Joshua P.,Diskin, Glenn S.,Velazco, Voltaire A.,Gr Copernicus GmbH 2018 Atmospheric measurement techniques Vol.11 No.4
<P><p><strong>Abstract.</strong> Since the late 1990s, the meteorological observatory established in Anmyeondo (36.5382°<span class='thinspace'></span>N, 126.3311°<span class='thinspace'></span>E, and 30<span class='thinspace'></span>m above mean sea level) has been monitoring several greenhouse gases such as CO<sub>2</sub>, CH<sub>4</sub>, N<sub>2</sub>O, CFCs, and SF<sub>6</sub> as a part of the Global Atmosphere Watch (GAW) Program. A high resolution ground-based (g-b) Fourier transform spectrometer (FTS) was installed at this observation site in 2013 and has been operated within the frame work of the Total Carbon Column Observing Network (TCCON) since August 2014. The solar spectra recorded by the g-b FTS cover the spectral range 3800 to 16<span class='thinspace'></span>000<span class='thinspace'></span>cm<sup>−1</sup> at a resolution of 0.02<span class='thinspace'></span>cm<sup>−1</sup>. In this work, the GGG2014 version of the TCCON standard retrieval algorithm was used to retrieve total column average CO<sub>2</sub> and CH<sub>4</sub> dry mole fractions (XCO<sub>2</sub>, XCH<sub>4</sub>) and from the FTS spectra. Spectral bands of CO<sub>2</sub> (at 6220.0 and 6339.5<span class='thinspace'></span>cm<sup>−1</sup> center wavenumbers, CH<sub>4</sub> at 6002<span class='thinspace'></span>cm<sup>−1</sup> wavenumber, and O<sub>2</sub> near 7880<span class='thinspace'></span>cm<sup>−1</sup> ) were used to derive the XCO<sub>2</sub> and XCH<sub>4</sub>. In this paper, we provide comparisons of XCO<sub>2</sub> and XCH<sub>4</sub> between the aircraft observations and g-b FTS over Anmyeondo station. A comparison of 13 coincident observations of XCO<sub>2</sub> between g-b FTS and OCO-2 (Orbiting Carbon Observatory) satellite measurements are also presented for the measurement period between February 2014 and November 2017. OCO-2 observations are highly correlated with the g-b FTS measurements (<i>r</i><sup>2</sup> = 0.884) and exhibited a small positive bias (0.189<span class='thinspace'></span>ppm). Both data set capture seasonal variations of the target species with maximum and minimum values in spring and late summer, respectively. In the future, it is planned to further utilize the FTS measurements for the evaluation of satellite observations such as Greenhouse Gases Observing Satellite (GOSAT, GOSAT-2). This is the first report of the g-b FTS observations of XCO<sub>2</sub> species over the Anmyeondo station.</p> </P>
Park, Tae Jun,Kim, Ji Yeon,Oh, S. Paul,Kang, So Young,Kim, Bong Wan,Wang, Hee Jung,Song, Kye Yong,Kim, Hyoung Chin,Lim, In Kyoung Wiley Subscription Services, Inc., A Wiley Company 2008 Hepatology Vol.47 No.5
<P><B>Abstract</B></P><P>A functional and biochemical interaction of TIS21<SUP>/BTG2/PC3</SUP> with Forkhead box M1 (FoxM1), essential transcription factor for hepatocyte regeneration and a master regulator of mitotic gene expression, was explored. Growth of hepatocellular carcinoma (HCC), developed by a single injection of diethylnitrosamine (DEN), was the same in both the TIS21<SUP>+/+</SUP> and TIS21<SUP>−/−</SUP> mice until 6 months, whereas it was significantly higher in the TIS21<SUP>−/−</SUP> mice at 9 months. Expression of TIS21 was significantly lower in both human and murine HCCs than in the surrounding tissues. Forced expression of TIS21 impaired growth, proliferation, and tumorigenic potential of Huh7 cells. At the mechanistic level, TIS21 inhibited FoxM1 phosphorylation, a required modification for its activation, by reducing cyclin B1–cdk1 activity, examined by <I>in vitro</I> kinase assay and FoxM1 mutant analyses. These observations were further confirmed <I>in vivo</I> by the reciprocal control of TIS21 expression and FoxM1 phosphorylation in the diethylnitrosamine‐induced HCCs and TIS21<SUP>−/−</SUP> mouse embryonic fibroblast (MEF), in addition to increased expression of cyclin B1 and cdk1 activity. <I>Conclusion:</I> TIS21 negatively regulated hepatocarcinogenesis in part by disruption of the FoxM1–cyclin B1 regulatory loop, thereby inhibiting proliferation of transformed cells developed in mouse and human livers. (H<SMALL>EPATOLOGY</SMALL> 2008.)</P>
Generation of mice with a conditional and reporter allele for <i>Tmem100</i>
Moon, Eun‐,Hye,Kim, Mi‐,Jung,Ko, Keum Soun,Kim, Yoo Sung,Seo, Jiyoung,Oh, S. Paul,Lee, Young Jae Wiley Subscription Services, Inc., A Wiley Company 2010 Genesis Vol.48 No.11
<P><B>Abstract</B></P><P>Activin receptor‐like kinase 1 (<I>ACVRL1</I>; <I>ALK1</I>) is predominantly expressed in arterial endothelial cells and plays an important role in angiogenesis. <I>ACVRL1</I> mutations cause hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder for which the underlying mechanism is poorly understood. We have found that expression of transmembrane protein 100 (<I>Tmem100</I>) is downregulated in the lung of <I>Acvrl1</I>‐deficient mice; however, its function is unknown. To elucidate the role of <I>Tmem100</I> in vivo, we generated a conditional knockout allele for <I>Tmem100</I> in which exon3, containing the entire coding sequence, was flanked by <I>loxP</I> sequences. The targeted allele also possessed a <I>lacZ</I> reporter cassette in intron2 for visualization of <I>Tmem100</I> expression. We found that <I>Tmem100</I> was predominantly expressed in arterial endothelial cells of developing embryos. The conditional and reporter allele will be a useful resource to investigate the in vivo role of <I>Tmem100</I>, especially in angiogenesis. genesis 48:673–378, 2010. © 2010 Wiley‐Liss, Inc.</P>