›› 2010, Vol. 30 ›› Issue (6): 410-414.

• 论文 • 上一篇    下一篇

Breakdance斑马鱼杂合子的早衰表型研究

  

  1. 1.上海交通大学医学院附属瑞金医院,上海 200025;2.美国梅约医学院,罗切斯特,明尼苏达州 55905
  • 收稿日期:2010-07-02 出版日期:2010-06-30 发布日期:2010-06-30
  • 基金资助:
    上海市浦江人才计划(08PJ14081),上海市科委“创新行动计划”(091409017),国家自然科学基金(青年基金)(30900491)

Premature Aging in Zebrafish Heterozygous breakdance Mutant

  1. 1. Ruijin Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,200025, China;2. Mayo Clinic College ofMedicine, Rochester,MN 55905, USA
  • Received:2010-07-02 Online:2010-06-30 Published:2010-06-30

摘要: 目的 有心律失常表型的Breakdance突变斑马鱼(bretb218)已被证实是人类同源基因kcnh2的纯合子突变体.它的杂合子tb218+/-虽没有明显的心律失常表型,却表现出早衰的态势.本研究旨在了解该杂合子斑马鱼的早衰表型,建立衰老研究的脊椎动物模型,并为进一步探索kcnh2基因突变与早衰的关系奠定基础.方法 生存曲线记录斑马鱼的预期寿命:用脊柱弯曲度和脊柱弯曲比值2个参数评估斑马鱼形态学的改变;挑战性游泳耐力试验评估斑马鱼的运动能力;心电图检测电生理活动的改变.结果 杂合子tb218+/-斑马鱼的生存率从20月龄起急剧下降,至40月龄时仅为8%,远低于野生型斑马鱼的80%;tb218+/-斑马鱼与野生型斑马鱼的脊柱弯曲度差异从8月龄起开始显现,20月龄后更明显,32月龄tb218+/-斑马鱼的脊柱弯曲度与60月龄野生型斑马鱼相当;挑战性游泳耐力试验发现,8月龄和20月龄tb218+/-斑马鱼的运动能力与野生型相当,但在32月龄时,其运动能力较同龄野生型斑马鱼降低56.44%;心电图检测发现,tb218+/-斑马鱼的心率随年龄增长而下降的幅度较野生型大,QTc间期在各月龄段均略长于野生型,尤其在8月龄时,但并未发现随月龄增长而延长的趋势.结论 杂合子tb218+/-斑马鱼呈现早衰态势,包括生存期缩短,脊柱弯曲早现,运动能力下降,心率随月龄增长的下降幅度增大及部分月龄段的QTc间期明显延长;这些表型可能与kcnh2基因的突变相关;该鱼系有望成为早衰研究的颇有价值的脊椎动物模型.

关键词: 斑马鱼, breakdance突变, 脊柱弯曲度, 挑战性游泳耐力试验, 心电图

Abstract: Objcctivc The breakdance-mutation (bretb 218) has been described as a mutation in the zebrafish orthologe of the human ether-a-go-go-related gene (HERG,kcnh2) with an arrhythmic heart beat in the homozygous. Interestingly, we found the heterozygous (hets) could generate multiple premature aging-like features and distinct electrophysiology. It made possible to develop a vertebrate model for study on premature aging associated to kcnh2. Methods Life span and body shape change were followed up and recorded. Exercise endurance capacity was examined by swim test. ECG test was performed in wild type (WT) and the hets at different adult stages. Results Survival rate dramatically descended and curly body showed from 20 months in the hets. ECG test showed heart rate dramatically decreased along aging process and QTc duration prolonged in the hets. Exercise endurance capacity significantly reduced 56.44% in the hets at 32 months comparing to WT at the same stage.Conclusion The heterozygous breib 218 has shorter life span and showed the presenility on appearance, electrophysiology and the exercise endurance capacity which may associate to the mutation in one allele of zebrafish orthologue of kcnh2.

Key words: Zebrafish, Breakdance-mutation;Spinal curvature, Exercise endurance capacity, ECG