A Novel Zak Knockout Mouse with a Defective Ribotoxic Stress Response.
A Novel Zak Knockout Mouse with a Defective Ribotoxic Stress Response.
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DOI：
10.3390/toxins8090259
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发表时间：
2016-09-02
期刊：
影响因子：
4.2
通讯作者：
Thorpe CM
中科院分区：
文献类型：
--
作者：
Jandhyala DM;Wong J;Mantis NJ;Magun BE;Leong JM;Thorpe CM
Ricin activates the proinflammatory ribotoxic stress response through the mitogen activated protein 3 kinase (MAP3K) ZAK, resulting in activation of mitogen activated protein kinases (MAPKs) p38 and JNK1/2. We had a novel zak−/− mouse generated to study the role of ZAK signaling in vivo during ricin intoxication. To characterize this murine strain, we intoxicated zak−/− and zak+/+ bone marrow–derived murine macrophages with ricin, measured p38 and JNK1/2 activation by Western blot, and measured zak, c-jun, and cxcl-1 expression by qRT-PCR. To determine whether zak−/− mice differed from wild-type mice in their in vivo response to ricin, we performed oral ricin intoxication experiments with zak+/+ and zak−/− mice, using blinded histopathology scoring of duodenal tissue sections to determine differences in tissue damage. Unlike macrophages derived from zak+/+ mice, those derived from the novel zak−/− strain fail to activate p38 and JNK1/2 and have decreased c-jun and cxcl-1 expression following ricin intoxication. Furthermore, compared with zak+/+ mice, zak−/− mice have decreased duodenal damage following in vivo ricin challenge. zak−/− mice demonstrate a distinct ribotoxic stress–associated phenotype in response to ricin and therefore provide a new animal model for in vivo studies of ZAK signaling.
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影响因子：
5.5
作者：
Cherla, Rama P.;Lee, Sang-Yun;Tesh, Vernon L.
通讯作者：
Tesh, Vernon L.
影响因子：
16.6
作者：
Liu, Jinfeng;McCleland, Mark;Stawiski, Eric W.;Gnad, Florian;Mayba, Oleg;Haverty, Peter M.;Durinck, Steffen;Chen, Ying-Jiun;Klijn, Christiaan;Jhunjhunwala, Suchit;Lawrence, Michael;Liu, Hanbin;Wan, Yinan;Chopra, Vivek;Yaylaoglu, Murat B.;Yuan, Wenlin;Ha, Connie;Gilbert, Houston N.;Reeder, Jens;Pau, Gregoire;Stinson, Jeremy;Stern, Howard M.;Manning, Gerard;Wu, Thomas D.;Neve, Richard M.;de Sauvage, Frederic J.;Modrusan, Zora;Seshagiri, Somasekar;Firestein, Ron;Zhang, Zemin
通讯作者：
Zhang, Zemin
影响因子：
4.4
作者：
Lindauer, Meghan L.;Wong, John;Magun, Bruce E.
通讯作者：
Magun, Bruce E.
影响因子：
3.7
作者：
Flora, Alyssa D.;Teel, Louise D.;O'Brien, Alison D.
通讯作者：
O'Brien, Alison D.
DOI：
10.1073/pnas.91.3.947
发表时间：
1994-02-01
影响因子：
11.1
作者：
POTHOULAKIS, C;CASTAGLIUOLO, I;LEEMAN, SE
通讯作者：
LEEMAN, SE