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Lipid transfection constructs Graves model in mice and 11C-CFT PET striatal imaging

Author: LongWen
Tutor: LiFang
School: Beijing Union Medical College
Course: Clinical
Keywords: Graves’ disease animal model gene engineering Positronemission tomography dopamine transporter
CLC: R-332
Type: PhD thesis
Year: 2012
Downloads: 15
Quote: 0
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Abstract


Graves’disease is a common and autoimmune related thyroid disease, yet some of its features remain enigmatic. There has been a major improvement in the devel-opment of animal models of Graves’disease, but none of them has been proved to be applicable, economic and effective. Further more, abnormal thyroid function is often related to emotional state, which per se is regulated by the striatum dopaminergic system. In our study, lipofection was employed to induce mouse model of Graves’ disease, and the best combination of its components was researched. Besides, possi-bility of detecting changes in striatum dopaminergic function in these animal models was also covered.There was two main parts of this study. The first part used different combina-tions of plasmid vectors, target genes and frequency of transfection to induce Graves disease. Changes of animal weight, thyroid hormone levels and levels of anti-thyroid hormone receptor (TSHR) antibodies (TRAbs) were compared with control group. The result suggested that either genes encoding TSHR or TSHR A subnit (THRA) was employed, no sufficient Graves’disease was induced by using the vector pUBC. On the contrary, when pCDNA3.1(+) was used as the vector, sufficient Graves’dis-ease was induced in both groups using TSHR and THRA subunit as target genes, the latter with an even higher effective rate. Further more, more frequent transfection in the early period was proved to be beneficial.In the second part,8representative animals in each group (pCDNA3.1(+)-TSHR, pCDNA3.1(+)-TSHRA and control) were enrolled.11C-CFT PET was used to evaluate changes in striatum dopaminergic function between these groups. Accord-ing to relatively small sample size, no statistical analysis was carried out effectively, but we can still find some clue that animals transfected with genes of TSHR or THRA subunit had lower activity of striatum dopamine transporter, and the extent was inversely correlated to serum free T4level.In brief, an economic and effective method to develop Graves’disease in mouse was introduced in this study, and using molecular imaging as a tool for evaluating changes in striatum dopaminergic function in this model was proved to be applicable.

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