Transmission of elk and deer prions to transgenic mice
Transmission of elk and deer prions to transgenic mice
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DOI：
10.1128/jvi.00098-06
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发表时间：
2006-09-01
影响因子：
5.4
通讯作者：
Prusiner, Stanley B.
中科院分区：
文献类型：
--
作者：
Tamguney, Gultekin;Giles, Kurt;Prusiner, Stanley B.
慢性消耗性疾病（CWD）是鹿和麋鹿的一种致命性朊病毒疾病。它是朊病毒疾病中的一种独特疾病，在圈养和自由放养的动物中传播。为了促进慢性消耗病朊病毒的生物学研究，我们产生了五个行的转基因（Tg）小鼠表达朊蛋白（PrP）从落基山麋鹿（马鹿），表示Tg（ElkPrP），和两个行的Tg小鼠表达PrP共同的白尾鹿（Odocoileus virginianus）和黑尾鹿（Odocoileus hemionus），表示Tg（DePrP）。Tg（ElkPrP）或Tg（DePrP）小鼠在超过600日龄时均未表现出自发性神经功能障碍。从CWD阳性麋鹿，白尾鹿，黑尾鹿脑样品产生的疾病在Tg（ElkPrP）小鼠接种后180和200天之间，在Tg（DePrP）小鼠300和400天之间。8只鹿脑接种物之一在540天内将疾病传播给过表达野生型小鼠PrP-A的Tg（MoPrP）4053小鼠。神经病理学分析显示，丰富的PrP淀粉样蛋白斑块在患病小鼠的大脑。来自有症状的Tg（ElkPrP）小鼠的脑匀浆在Tg（ElkPrP）小鼠中在120至190天内产生疾病。与Tg（ElkPrP）和Tg（DePrP）小鼠相反，过表达人、牛或绵羊PrP的Tg小鼠在接种来自9种不同分离株的CWD朊病毒后> 500天未发生朊病毒疾病。这些发现表明，麋鹿、黑尾鹿和白尾鹿的慢性消耗病朊病毒可以很容易地在这三种鹿科动物之间传播。
Chronic wasting disease (CWD) is a fatal prion disease in deer and elk. Unique among the prion diseases, it is transmitted among captive and free-ranging animals. To facilitate studies of the biology of CWD prions, we generated five lines of transgenic (Tg) mice expressing prion protein (PrP) from Rocky Mountain elk (Cervus elaphus nelsoni), denoted Tg(ElkPrP), and two lines of Tg mice expressing PrP common to white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus), denoted Tg(DePrP). None of the Tg(ElkPrP) or Tg(DePrP) mice exhibited spontaneous neurologic dysfunction at more than 600 days of age. Brain samples from CWD-positive elk, white-tailed deer, and mule deer produced disease in Tg(ElkPrP) mice between 180 and 200 days after inoculation and in Tg(DePrP) mice between 300 and 400 days. One of eight cervid brain inocula transmitted disease to Tg(MoPrP)4053 mice overexpressing wild-type mouse PrP-A in similar to 540 days. Neuropathologic analysis revealed abundant PrP amyloid plaques in the brains of ill mice. Brain homogenates from symptomatic Tg(ElkPrP) mice produced disease in 120 to 190 days in Tg(ElkPrP) mice. In contrast to the Tg(ElkPrP) and Tg(DePrP) mice, Tg mice overexpressing human, bovine, or ovine PrP did not develop prion disease after inoculation with CWD prions from among nine different isolates after > 500 days. These findings suggest that CWD prions from elk mule deer, and white-tailed deer can be readily transmitted among these three cervid species.