CAJ | 학술논문

目的探讨唐氏综合征导致智力低下的分子机制.方法采用Ts65Dn小鼠作为唐氏综合征小鼠模型,周龄3～12周的雌雄鼠各3只,按雌雄比例1∶1合笼传代繁殖.第1代生育存活的17只新生小鼠中,保持了Ts65Dn 三体型别和正常型别小鼠分别为5只(Ts65Dn组)和12只,后者中随机选取5只为对照组,常规饲养至16～18周.采用同位素标记相对和绝对定量(isobarictags for relative and absolute quantitation,iTRAQ)技术,筛选海马组织中差异蛋白,比较2组差异蛋白的表达.结果 2组小鼠的海马组织中共鉴定到蛋白质2805个,其中差异有统计学意义的蛋白共374个.与对照组相比,Ts65Dn小鼠海马组织中表达上调的蛋白195个,表达下调的179个.按P值由低到高排序,P值最低的7种蛋白质为C2orf47同源蛋白、细丝蛋白A1作用蛋白亚型2、锌指蛋白、中心体基质蛋白亚型1、SEC23作用蛋白、BAG分子伴侣蛋白3和丝氨酸蛋白酶抑制剂1.结论 Ts65Dn小鼠海马组织存在差异蛋白表达,可能与其神经缺陷密切相关.iTRAQ技术有助于筛选及鉴定海马组织中的差异蛋白.
목적 탐토당씨종합정도치지력저하적분자궤제.방법 채용Ts65Dn소서작위당씨종합정소서모형,주령3～12주적자웅서각3지,안자웅비례1∶1합롱전대번식.제1대생육존활적17지신생소서중,보지료Ts65Dn 삼체형별화정상형별소서분별위5지(Ts65Dn조)화12지,후자중수궤선취5지위대조조,상규사양지16～18주.채용동위소표기상대화절대정량(isobarictags for relative and absolute quantitation,iTRAQ)기술,사선해마조직중차이단백,비교2조차이단백적표체.결과 2조소서적해마조직중공감정도단백질2805개,기중차이유통계학의의적단백공374개.여대조조상비,Ts65Dn소서해마조직중표체상조적단백195개,표체하조적179개.안P치유저도고배서,P치최저적7충단백질위C2orf47동원단백、세사단백A1작용단백아형2、자지단백、중심체기질단백아형1、SEC23작용단백、BAG분자반려단백3화사안산단백매억제제1.결론 Ts65Dn소서해마조직존재차이단백표체,가능여기신경결함밀절상관.iTRAQ기술유조우사선급감정해마조직중적차이단백.
Objective To explore the molecular mechanism of hypophrenia induced by Down syndrome (DS).Methods Ts65Dn mice were used as DS animal model.Three female mice and three male mice of three to twelve weeks old were mated.Among the 17 first-generation mice alive,five mice remained Ts65Dn trisomy and 12 mice were normal.Five Ts65Dn mice and five normal mice were selected randomly as Ts65Dn group and control group,and bred till 16 to 18 weeks old for experiments.Differential proteins in hippocampus of mice were tested by isobaric tags for relative and absolute quantitation (iTRAQ).Expressions of the differential proteins in Ts65Dn group were detected compared with those in control group.Results A total of 2805 proteins were identified in hippocampus of Ts65Dn group and control group,and significant differences were observed in the expressions of 374 proteins.Compared with those in control group,expressions of 195 proteins increased and 179 reduced in Ts65Dn group.Sorted by P value from low to high,the seven proteins with the lowest P value were uncharacterized protein C2orf47 homolog,isoform 2 of filamin A-interacting protein 1-like,zinc finger protein,isoform 1 of pericentriolar material 1 protein,SEC23 interacting protein,BAG family molecular chaperone regulator 3 and serpin H1.Conclusions Differential proteins are observed in hippocampus of Ts65Dn mice,perhaps closely correlating to neurological defects.The new technology of iTRAQ helps to screen and identify differential proteins in hippocampus.