| First Author | Jandhyala DM | Year | 2016 |
| Journal | Toxins (Basel) | Volume | 8 |
| Issue | 9 | PubMed ID | 27598200 |
| Mgi Jnum | J:241322 | Mgi Id | MGI:5901799 |
| Doi | 10.3390/toxins8090259 | Citation | Jandhyala DM, et al. (2016) A Novel Zak Knockout Mouse with a Defective Ribotoxic Stress Response. Toxins (Basel) 8(9) |
| abstractText | 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. |
