Development of transgenic mouse models for the study of human olfactory dysfunction

Development of transgenic mouse models for the study of human olfactory dysfunction
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DOI:
10.1177/194589240501900302
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发表时间:
2005-05-01
期刊:
AMERICAN JOURNAL OF RHINOLOGY
影响因子:
--
通讯作者:
Reed, RR
Reed, RR
中科院分区:
其他
文献类型:
--
作者:
Lane, AP;Zhao, HQ;Reed, RR

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背景:嗅觉丧失是一个重大的健康问题,但目前尚不完全清楚。开发合适的动物模型对于人类嗅觉丧失研究的进展至关重要。转基因技术的最新进展允许创建模型系统来解决嗅觉神经元功能障碍的原因。方法:本综述描述了两种在嗅觉丧失研究中具有潜在用途的转基因小鼠模型,并强调了此类系统开发的分子技术。结果:使用标准分子生物学技术生成的遗传构建体通过同源重组或随机整合引入小鼠种系。一种构建体 (UbI7) 将嗅觉受体 17 置于嗅觉标记蛋白启动子的控制之下。另外两种构建体 (TI) 共同作用,直接在嗅觉上皮细胞中表达细胞因子,创造了一种研究炎症性嗅觉丧失的新方法。结论:现在存在强大的科学工具来开发可用于研究人类嗅觉疾病的动物模型。 UbI7 小鼠品系的转基因嗅觉神经元将对已知的气味做出反应,从而促进体外检查嗅觉神经元功能调节的实验。 TI小鼠嗅粘膜表达特定基因的能力在阐明细胞因子在体内嗅觉功能障碍发展中的作用方面具有巨大潜力。
Background: Olfactory loss is a significant health problem that remains incompletely understood. The development of suitable animal models is essential to the progress of human olfactory loss research. Recent advancements in transgenic technology allow the creation of model systems to address causes of olfactory neuron dysfunction.Methods: This review describes two transgenic mouse models with potential usefulness in the study of olfactory loss and highlights the molecular techniques that underlie the development of such systems.Results: Genetic constructs generated using standard molecular biological techniques are introduced into mouse germ lines either by homologous recombination or by random integration. One construct (UbI7) places the olfactory receptor 17 under control of the olfactory marker protein promoter. The other two constructs (TI) act together to direct expression of cytokines in the olfactory epithelium, creating a novel approach to the study of inflammatory olfactory loss.Conclusions: Powerful scientific tools now exist to develop animal models useful to the study of human olfactory disease. Transgenic olfactory neurons from the UbI7 mouse strain will respond to known odorants, facilitating experiments that examine in vitro modulation of olfactory neuron function. The ability to express specific genes in the olfactory mucosa of the TI mouse has great potential in elucidating the role of cytokines in the development of olfactory dysfunction in vivo.