学术探索
学术期刊
学术作者
新闻热点
数据分析
智能评审

Targeted disruption of Adamts16 gene in a rat genetic model of hypertension

被引：61
作者：
Gopalakrishnan, Kathirvel [1 ,2 ]
Kumarasamy, Sivarajan [1 ,2 ]
Abdul-Majeed, Shakila [1 ,2 ]
Kalinoski, Andrea L. [1 ,3 ]
Morgan, Eric E. [2 ,4 ]
Gohara, Amira F. [5 ]
Nauli, Surya M. [1 ,6 ]
Filipiak, Wanda E. [7 ]
Saunders, Thomas L. [7 ]
Joe, Bina [1 ,2 ]
机构：
[1] Univ Toledo, Coll Med & Life Sci, Ctr Hypertens & Personalized Med, Toledo, OH 43614 USA
[2] Univ Toledo, Coll Med & Life Sci, Dept Physiol & Pharmacol, Toledo, OH 43614 USA
[3] Univ Toledo, Coll Med & Life Sci, Dept Surg, Toledo, OH 43614 USA
[4] Univ Toledo, Coll Med & Life Sci, Ctr Diabet & Endocrine Res, Toledo, OH 43614 USA
[5] Univ Toledo, Coll Med & Life Sci, Dept Pathol, Toledo, OH 43614 USA
[6] Univ Toledo, Coll Pharm, Dept Pharmacol, Toledo, OH 43614 USA
[7] Univ Michigan, Sch Med, Transgen Anim Model Core, Ann Arbor, MI 48109 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 50期
基金：
美国国家卫生研究院;
关键词：
congenic; mapping; ZFN mutant; quantitative trait locus; GWAS; BLOOD-PRESSURE QTL; CONGENIC STRAINS; LINKAGE ANALYSIS;
D O I：
10.1073/pnas.1211290109
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要：
A disintegrin-like metalloproteinase with thrombospondin motifs-16 (Adamts16) is an important candidate gene for hypertension. The goal of the present study was to further assess the candidacy of Adamts16 by targeted disruption of this gene in a rat genetic model of hypertension. A rat model was generated by manipulating the genome of the Dahl Salt-sensitive (S) rat using zinc-finger nucleases, wherein the mutant rat had a 17 bp deletion in the first exon of Adamts16, introducing a stop codon in the transcript. Systolic blood pressure (BP) of the homozygous Adamts16(mutant) rats was lower by 36 mmHg compared with the BP of the S rats. The Adamts16mutant rats exhibited significantly lower aortic pulse wave velocity and vascular media thickness compared with S rats. Scanning electron and fluorescence microscopic studies indicated that the mechanosensory cilia of vascular endothelial cells from the Adamts16(mutant) rats were longer than that of the S rats. Furthermore, Adamts16(mutant) rats showed splitting and thickening of glomerular capillaries and had a longer survival rate, compared with the S rats. Taken together, these physiological observations functionally link Adamts16 to BP regulation and suggest the vasculature as the potential site of action of Adamts16 to lower BP.
引用
收藏
页码：20555 / 20559
页数：5
相关论文
共 24 条
[1]
Dopamine Receptor Type 5 in the Primary Cilia Has Dual Chemo- and Mechano-Sensory Roles [J].
Abdul-Majeed, Shakila ;
Nauli, Surya M. .
HYPERTENSION, 2011, 58 (02) :325-U406
[2]
The genetic dissection of essential hypertension [J].
Cowley, Allen W., Jr. .
NATURE REVIEWS GENETICS, 2006, 7 (11) :829-840
[3]
Report of the National Heart, Lung, and Blood Institute Working Group on Epigenetics and Hypertension [J].
Cowley, Allen W., Jr. ;
Nadeau, Joseph H. ;
Baccarelli, Andrea ;
Berecek, Kathleen ;
Fornage, Myriam ;
Gibbons, Gary H. ;
Harrison, David G. ;
Liang, Mingyu ;
Nathanielsz, Peter W. ;
O'Connor, Daniel T. ;
Ordovas, Jose ;
Peng, Weiqun ;
Soares, Marcelo Bento ;
Szyf, Moshe ;
Tolunay, H. Eser ;
Wood, Katherine C. ;
Zhao, Keji ;
Galis, Zorina S. .
HYPERTENSION, 2012, 59 (05) :899-905
[4]
Increased Expression of NAD(P)H Oxidase Subunit p67phox in the Renal Medulla Contributes to Excess Oxidative Stress and Salt-Sensitive Hypertension [J].
Feng, Di ;
Yang, Chun ;
Geurts, Aron M. ;
Kurth, Terry ;
Liang, Mingyu ;
Lazar, Jozef ;
Mattson, David L. ;
O'Connor, Paul M. ;
Cowley, Allen W., Jr. .
CELL METABOLISM, 2012, 15 (02) :201-208
[5]
Advances in transgenic rat production [J].
Filipiak, Wanda E. ;
Saunders, Thomas L. .
TRANSGENIC RESEARCH, 2006, 15 (06) :673-686
[6]
Rearranging Exosites in Noncatalytic Domains Can Redirect the Substrate Specificity of ADAMTS Proteases [J].
Gao, Weiqiang ;
Zhu, Jian ;
Westfield, Lisa A. ;
Tuley, Elodee A. ;
Anderson, Patricia J. ;
Sadler, J. Evan .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (32) :26944-26952
[7]
Genome scan and congenic strains for blood pressure QTL using Dahl salt-sensitive rats [J].
Garrett, MR ;
Dene, H ;
Walder, R ;
Zhang, QY ;
Cicila, GT ;
Assadnia, S ;
Deng, AY ;
Rapp, JP .
GENOME RESEARCH, 1998, 8 (07) :711-723
[8]
Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases [J].
Geurts, Aron M. ;
Cost, Gregory J. ;
Freyvert, Yevgeniy ;
Zeitler, Bryan ;
Miller, Jeffrey C. ;
Choi, Vivian M. ;
Jenkins, Shirin S. ;
Wood, Adam ;
Cui, Xiaoxia ;
Meng, Xiangdong ;
Vincent, Anna ;
Lam, Stephen ;
Michalkiewicz, Mieczyslaw ;
Schilling, Rebecca ;
Foeckler, Jamie ;
Kalloway, Shawn ;
Weiler, Hartmut ;
Menoret, Severine ;
Anegon, Ignacio ;
Davis, Gregory D. ;
Zhang, Lei ;
Rebar, Edward J. ;
Gregory, Philip D. ;
Urnov, Fyodor D. ;
Jacob, Howard J. ;
Buelow, Roland .
SCIENCE, 2009, 325 (5939) :433-433
[9]
Augmented Rififylin Is a Risk Factor Linked to Aberrant Cardiomyocyte Function, Short-QT Interval and Hypertension [J].
Gopalakrishnan, Kathirvel ;
Morgan, Eric E. ;
Yerga-Woolwine, Shane ;
Farms, Phyllis ;
Kumarasamy, Sivarajan ;
Kalinoski, Andrea ;
Liu, Xiaochen ;
Wu, Jian ;
Liu, Lijun ;
Joe, Bina .
HYPERTENSION, 2011, 57 (04) :764-+
[10]
Substitution mapping of a blood pressure quantitative trait locus to a 2.73 Mb region on rat chromosome 1 [J].
Joe, B ;
Garrett, MR ;
Dene, H ;
Rapp, JP .
JOURNAL OF HYPERTENSION, 2003, 21 (11) :2077-2084
123