清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Efficiency and functional consequences of adenovirus-mediated in vivo gene transfer to normal and dystrophic (mdx) mouse diaphragm.

肌营养不良蛋白 杜氏肌营养不良 mdx鼠标 转基因 振膜(声学) 肌营养不良 体内 生物 遗传增强 收缩性 内科学 内分泌学 细胞生物学 医学 基因 遗传学 扬声器 物理 声学
作者
Basil J. Petrof,Gyula Acsádi,Ágnes Jáni,Bernard Massie,Johanne Bourdon,Neola Matusiewicz,Liying Yang,Hanns Lochmüller,George Karpati
出处
期刊:American Journal of Respiratory Cell and Molecular Biology [American Thoracic Society]
卷期号:13 (5): 508-517 被引量:34
标识
DOI:10.1165/ajrcmb.13.5.7576685
摘要

The protein dystrophin is absent in muscles of patients with Duchenne muscular dystrophy (DMD) as well as in mdx mice. The mdx mouse diaphragm closely resembles the human DMD phenotype and should serve as an appropriate model for future studies of dystrophin gene replacement. In this regard, recombinant adenovirus (AV) holds great promise as a vector for delivering a functional dystrophin gene to muscle. However, the use of AV is hampered by the development of an immune response against transduced cells, resulting in short-lived transgene expression as well as possible adverse effects on organ function. In the present study, sensitive reporter genes were employed to determine the efficiency and functional consequences of AV-mediated gene transfer to the diaphragm in both normal and mdx adult mice. One week after direct intramuscular injection of AV into the diaphragm, the level of transgene expression was significantly increased in mdx compared with normal diaphragms. In addition, small-caliber fibers (< 500 microns2) demonstrated preferential transduction in both groups of mice. Normal diaphragms receiving AV exhibited a substantial reduction in maximal twitch and tetanic force generation, whereas no significant effect on diaphragm contractility was found in the mdx group at 1 wk after injection. At 1 mo after AV administration, however, there was a significant decrease in force production by both normal and mdx diaphragms. Immunosuppression with cyclosporine A over 1 mo did not augment the level of transgene expression, but a beneficial effect on diaphragm force-generating capacity was observed in both groups of animals. We conclude the following: (1) short-term transduction of the diaphragm is more efficient in mdx than in normal mice; (2) AV leads to reduced force production by the diaphragm, with this effect being more pronounced in normal than in mdx in the early (but not the late) postinjection period; and (3) immunosuppressive therapy with cyclosporine has a partially protective effect on muscle function after AV administration, which is apparently unrelated to sparing of transduced fibers from elimination by the host immune system. These findings have important implications for the application of AV-mediated dystrophin gene transfer to the treatment of DMD.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
5秒前
有魅力荟发布了新的文献求助10
10秒前
缥缈的闭月完成签到,获得积分10
16秒前
echo完成签到 ,获得积分10
40秒前
回首不再是少年完成签到,获得积分0
44秒前
jasmine完成签到 ,获得积分10
1分钟前
吉祥高趙完成签到 ,获得积分10
1分钟前
小小果妈完成签到 ,获得积分10
1分钟前
奶糖喵完成签到 ,获得积分10
1分钟前
hbuhfl完成签到 ,获得积分10
1分钟前
一彤展翅完成签到,获得积分10
1分钟前
1分钟前
xun发布了新的文献求助10
1分钟前
ally完成签到,获得积分10
1分钟前
li完成签到 ,获得积分10
2分钟前
kenchilie完成签到 ,获得积分10
2分钟前
属实有点拉胯完成签到 ,获得积分10
2分钟前
apckkk完成签到 ,获得积分10
2分钟前
3分钟前
SciKid524完成签到 ,获得积分10
3分钟前
chemlixy完成签到 ,获得积分10
3分钟前
cstp完成签到,获得积分10
3分钟前
mark33442完成签到,获得积分10
3分钟前
小美酱完成签到 ,获得积分10
3分钟前
淡然藏花完成签到 ,获得积分10
3分钟前
苏su完成签到 ,获得积分10
4分钟前
完美梨愁完成签到 ,获得积分10
4分钟前
苗条的小蜜蜂完成签到 ,获得积分10
4分钟前
爱撒娇的紫菜完成签到,获得积分10
4分钟前
zhao完成签到,获得积分10
4分钟前
4分钟前
4分钟前
Kristina完成签到,获得积分10
4分钟前
雪山飞龙完成签到,获得积分10
4分钟前
小乙猪完成签到 ,获得积分0
4分钟前
赘婿应助科研通管家采纳,获得10
4分钟前
charliechen完成签到 ,获得积分10
4分钟前
有魅力荟完成签到,获得积分20
5分钟前
keyan完成签到 ,获得积分10
5分钟前
Connie完成签到,获得积分10
5分钟前
高分求助中
Continuum Thermodynamics and Material Modelling 3000
Production Logging: Theoretical and Interpretive Elements 2700
Les Mantodea de Guyane Insecta, Polyneoptera 1000
Structural Load Modelling and Combination for Performance and Safety Evaluation 1000
Conference Record, IAS Annual Meeting 1977 820
電気学会論文誌D(産業応用部門誌), 141 巻, 11 号 510
Typology of Conditional Constructions 500
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3571317
求助须知:如何正确求助?哪些是违规求助? 3141926
关于积分的说明 9444838
捐赠科研通 2843331
什么是DOI,文献DOI怎么找? 1562830
邀请新用户注册赠送积分活动 731326
科研通“疑难数据库(出版商)”最低求助积分说明 718524