摘要
果蝇心脏一直以来都是研究心血管发育的极好模型,许多控制心脏分化和特化的调控基因和信号途径从果蝇到哺乳动物都是保守的.由于近年心力衰竭的发病率不断升高,我们最近又建立了果蝇心力衰竭模型用于大规模筛选和鉴定心力衰竭的相关基因.在这个模型中,适龄的成体果蝇被整齐排列在导电的载玻片上,通过电极短暂刺激30s,使果蝇的心跳频率由正常的3Hz增加到6Hz,停止后检测果蝇心率恢复情况,不能恢复正常心跳频率或出现纤维性震颤的果蝇视为心力衰竭.该模型可以在短期内大规模筛选到与心力衰竭相关的基因.利用此心力衰竭模型,我们筛选了164个果蝇2号染色体缺失系,获得33个候选缺失系.这些候选缺失系的心衰率要么与野生型品系相比差异显著,要么与tinman或panier突变系相比差异显著,提示这些缺失系中可能含有与心力衰竭相关的调控基因.
The Drosophila heart has been an excellent model of cardiovascular development for over a decade,many of the regulatory genes and signal pathways controlling the specification and differentiation of the cardiac progenitors are conserved from Drosophila to vertebrates.Because heart failure are more common in recent years,we have recently developed an external electrical pacing paradigm to use the Drosophila heart to understand the molecular mechanisms underlying aging of cardiac tissue and their contribution to heart failure.In this model,Drosophila adults are aligned on a specially prepared conductive glass slide and stimulated by a standard square wave stimulator to accelerate their heart rate,which at rest is 3 Hz,to 6 Hz for 30 seconds.When the current pulses are turned off,the flies will either recover to regular heartbeat or fibrillate or undergo arrest.This assay provides to conduct large-scale genetic screens for loci that affect cardiac performance in an age-related manner.Taking advantage of this model,164 of the 2nd chromosome deficiency lines of Drosophila were screened and 33 candidate deficiency lines were obtained,of which the heart failure rate was significant different either from that of wild type or tinman or panier mutants,indicating these deficiencies contain heart failure gene candidates.
出处
《生命科学研究》
CAS
CSCD
2010年第3期195-198,共4页
Life Science Research
基金
国家自然科学基金资助项目(30930054
30900851)
湖南省普通高校学科带头人培养计划(湘教通2008-315)
关键词
果蝇模型
心力衰竭
2号染色体缺失系
调控基因
Drosophila model
heart failure
the 2nd chromosome deficiency lines
regulatory genes
