Adenovirus serotype 35 vector-mediated transduction into human CD46-transgenic mice
Adenovirus serotype 35 vector-mediated transduction into human CD46-transgenic mice
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DOI：
10.1038/sj.gt.3302749
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发表时间：
2006-07-01
期刊：
影响因子：
5.1
通讯作者：
Mizuguchi, H.
中科院分区：
文献类型：
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作者：
Sakurai, F.;Kawabata, K.;Mizuguchi, H.
我们之前证明，对小鼠全身施用腺病毒血清型 35 (Ad35) 载体并不能介导器官中的有效转导，可能是因为 B 亚组 Ad 受体的小鼠类似物、人 CD46（膜辅因子蛋白）的表达仅限于睾丸。在这里，我们使用普遍表达人 CD46 的纯合和半合人 CD46 转基因 (CD46TG) 小鼠描述了 Ad35 载体的体外和体内转导特性。 Ad35 载体比野生型小鼠更有效地转导 CD46TG 小鼠制备的原代树突状细胞和巨噬细胞。体内转导实验表明，CD46TG 小鼠比野生型小鼠更容易受到 Ad35 载体介导的体内转导的影响。特别是，与半合子CD46TG小鼠相比，纯合子CD46TG小鼠在器官中表达更高水平的CD46，在腹膜内施用后往往表现出比半合子CD46TG小鼠更高的转导效率。 Ad35载体的腹膜内施用导致纯合CD46TG小鼠腹膜器官间皮细胞的有效转导。这些结果表明 Ad35 载体将人 CD46 识别为 CD46TG 小鼠的细胞受体。然而，Ad35载体在CD46TG小鼠体内的体内转导效率远低于常规Ad5载体在野生型小鼠体内的转导效率。
We previously demonstrated that systemic administration of adenovirus serotype 35 ( Ad35) vectors to mice does not mediate efficient transduction in organs, probably because expression of the mouse analog of the subgroup B Ad receptor, human CD46 ( membrane cofactor protein), is limited to the testis. Here, we describe the in vitro and in vivo transduction characteristics of Ad35 vectors by using homozygous and hemizygous human CD46-transgenic ( CD46TG) mice, which ubiquitously express human CD46. An Ad35 vector more efficiently transduced the primary dendritic cells and macrophages prepared from CD46TG mice than those from wild-type mice. In vivo transduction experiments demonstrated that CD46TG mice are more susceptible to Ad35 vector-mediated in vivo transduction than are wild-type mice. In particular, homozygous CD46TG mice, which express higher levels of CD46 in the organs than hemizygous CD46TG mice, tend to exhibit higher transduction efficiencies after intraperitoneal administration than hemizygous CD46TG mice. Intraperitoneal administration of Ad35 vectors resulted in efficient transduction into the mesothelial cells of the peritoneal organs in homozygous CD46TG mice. These results indicate that an Ad35 vector recognizes human CD46 as a cellular receptor in CD46TG mice. However, the in vivo transduction efficiencies of Ad35 vectors in CD46TG mice are much lower than those of conventional Ad5 vectors in wild-type mice.