Targeted retroviral gene transfer into the rat biliary tract

Targeted retroviral gene transfer into the rat biliary tract
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DOI:
10.1007/bf02374373
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发表时间:
1996-01-01
期刊:
SOMATIC CELL AND MOLECULAR GENETICS
影响因子:
--
通讯作者:
Raper, SE
Raper, SE
中科院分区:
其他
文献类型:
--
作者:
Cabrera, JA;Wilson, JM;Raper, SE

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通过临时结扎胆管诱导增殖的能力表明,逆转录病毒介导的基因转移到胆道细胞中的假设是可以完成的。本文研究了Fischer F344雄性大鼠胆管分化的组织学变化、H-3-胸腺嘧啶核苷掺入和细胞因子-19免疫荧光染色的时程变化。将含有编码大肠杆菌P-半乳糖苷酶基因的重组长臂猿白血病病毒(GALV)导入24小时阻塞的胆管中。当病毒暴露在阻塞的管道中12h(类似于0.1%)时,基因转移最大。X-Gal阳性细胞主要分布在细胞因子19阴性的胆管周围组织,可见新生胆管的出现。这些数据表明,逆转录病毒感染梗阻的大鼠胆管的靶细胞可能是成熟的、完全分化的胆管上皮的前体细胞。
The ability to induce proliferation by temporary duct ligation suggested an hypothesis that retrovirus-mediated gene transfer into cells of the biliary tract could be accomplished. The time course of histologic changes, incorporation of H-3-thymidine and immunofluorescent staining with a monoclonal antibody to cytokevatin-19 (a marker for differentiated bile ducts) was studied in male Fischer F344 rats. A recombinant Gibbon ape leukemia virus (GALV), containing a gene encoding Escherichia coli P-galactosidase was next introduced into 24 hr obstructed bile ducts. Gene transfer was maximal when virus was exposed to the obstructed duct for 12 hr (similar to 0.1%). The majority of X-gal positive cells were in cytokevatin-19 negative peribiliary tissues, which had the appearance of newly forming bile ducts. The data suggest that cells targeted by retroviral infection of the obstructed rat bile duct may be a precursor of mature, fully differentiated biliary epithelium.