The N-methyl-D-aspartate receptor in heart development: A gene knockdown model using siRNA

被引:7
作者
Lie, Octavian V. [1 ]
Bennett, Gregory D. [1 ]
Rosenquist, Thomas H. [1 ]
机构
[1] Univ Nebraska, Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA
关键词
NMDA receptor; Electroporation; siRNA; NR1-subunit; Heart defects; Homocysteine; Chicken embryo; CARDIAC NEURAL CREST; NMDA RECEPTOR; TUBE DEFECTS; OROFACIAL CLEFTS; FOLIC-ACID; EXPRESSION; HOMOCYSTEINE; CELLS; RISK; CLONING;
D O I
10.1016/j.reprotox.2009.08.005
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Antagonists of the N-methyl-D-aspartate receptor (NMDAR) may disrupt the development of the cardiac neural crest (CNC) and contribute to conotruncal heart defects. To test this interaction, a loss-of-function model was generated using small interfering RNAs (siRNA) directed against the critical NR1-subunit of this receptor in avian embryos. The coding sequence of the chicken NR1 gene and predicted protein sequences were characterized and found to be homologous with other vertebrate species. Analysis of its spatiotemporal expression demonstrated its expression within the neural tube at pre-migratory CNC sites. siRNA targeted to the NR1-mRNA in pre-migratory CNC lead to a significant decrease in NR1 protein expression. However, embryo survival and heart development were not adversely affected. These results indicate that the CNC may function normally in the absence of functional NMDAR, and that NMDAR antagonists may have a complex impact upon the CNC that transcends impairment of a single receptor type. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:32 / 41
页数:10
相关论文
共 62 条
  • [1] DEATH IN INFANCY FROM UNRECOGNIZED CONGENITAL HEART-DISEASE
    ABUHARB, M
    HEY, E
    WREN, C
    [J]. ARCHIVES OF DISEASE IN CHILDHOOD, 1994, 71 (01) : 3 - 7
  • [2] Dextromethorphan and other N-methyl-D-aspartate receptor antagonists are teratogenic in the avian embryo model
    Andaloro, VJ
    Monaghan, DT
    Rosenquist, TH
    [J]. PEDIATRIC RESEARCH, 1998, 43 (01) : 1 - 7
  • [3] Failure of homocysteine to induce neural tube defects in a mouse model
    Bennett, GD
    VanWaes, J
    Moser, K
    Chaudoin, T
    Starr, L
    Rosenquist, TH
    [J]. BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY, 2006, 77 (02) : 89 - 94
  • [4] The expression of the NR1-subunit of the NMDA receptor during mouse and early chicken development
    Bennett, Gregory D.
    Moser, Kristine
    Chaudoin, Tammy
    Rosenquist, Thomas H.
    [J]. REPRODUCTIVE TOXICOLOGY, 2006, 22 (03) : 536 - 541
  • [5] Prevention of neural-tube defects with folic acid in China
    Berry, RJ
    Li, Z
    Erickson, JD
    Li, S
    Moore, CA
    Wang, H
    Mulinare, J
    Zhao, P
    Wong, LYC
    Gindler, J
    Hong, SX
    Correa, A
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (20) : 1485 - 1490
  • [6] Cardiac outflow tract malformations in chick embryos exposed to homocysteine
    Boot, MJ
    Steegers-Theunissen, RPM
    Poelmann, RE
    van Iperen, L
    Gittenberger-de Groot, AC
    [J]. CARDIOVASCULAR RESEARCH, 2004, 64 (02) : 365 - 373
  • [7] Effect of elevated homocysteine on cardiac neural crest migration in vitro
    Brauer, PR
    Rosenquist, TH
    [J]. DEVELOPMENTAL DYNAMICS, 2002, 224 (02) : 222 - 230
  • [8] Induction of Apoptosis of Human Colon Cancer Cells by siRNA Recombinant Expression Vector Targeting Survivin Gene
    Cai, Ming
    Wang, Guobin
    Tao, Kaixiong
    Cai, Changxue
    [J]. JOURNAL OF HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY-MEDICAL SCIENCES, 2009, 29 (01) : 45 - 49
  • [9] Site within N-methyl-D-aspartate receptor pore modulates channel Gating
    Chen, NS
    Li, B
    Murphy, TH
    Raymond, LA
    [J]. MOLECULAR PHARMACOLOGY, 2004, 65 (01) : 157 - 164
  • [10] Chen YX, 2004, MOL VIS, V10, P874