Finnell Richard H, Junker Wade M, Wadman Lisa Kvist, Cabrera Robert M
Institute of Biosciences and Technology, Texas A & M University System Health Science Center, Houston, TX 77030-3303, USA.
Neurochem Res. 2002 Oct;27(10):1165-80. doi: 10.1023/a:1020977409850.
The developing mammalian nervous system is subject to devastating congenital malformations with clinical significance that extends into the billions of health care dollars annually worldwide. Neural tube defects (NTDs) are among the most common of all human congenital defects, yet their etiology remains poorly understood. This is largely due to the complexity of the genetic factors regulating the intricate events involved in neurulation. Using mouse model systems and the application of modern molecular biological technologies, we have recently gained a greater appreciation for the factors that not only regulate normal neural tube closure (NTC), but those genetic factors that predispose an embryo to significant birth defects such as anencephaly or spina bifida. We have selected prominent murine mutants, both spontaneous and genetically modified, as well as the use of teratogenic agents, to examine the impact of altering the normal pattern of gene expression in the developing neural tube.
发育中的哺乳动物神经系统容易出现具有临床意义的毁灭性先天性畸形,其影响在全球范围内每年涉及数十亿美元的医疗保健费用。神经管缺陷(NTDs)是所有人类先天性缺陷中最常见的缺陷之一,但其病因仍知之甚少。这主要是由于调节神经胚形成过程中复杂事件的遗传因素十分复杂。利用小鼠模型系统并应用现代分子生物技术,我们最近对不仅调节正常神经管闭合(NTC)的因素,而且对使胚胎易患无脑儿或脊柱裂等重大出生缺陷的遗传因素有了更深入的认识。我们选择了突出的小鼠突变体,包括自发突变体和基因改造突变体,以及使用致畸剂,来研究改变发育中的神经管中正常基因表达模式的影响。