Kimberly Stark, Tatiana Goncharov, Eugene Varfolomeev, Luke Xie, Hai Ngu, Ivan Peng, Keith R Anderson, Erik Verschueren, Meena Choi, Donald S Kirkpatrick, Amy Easton, Joshua D Webster, Brent S McKenzie, Domagoj Vucic, Baris Bingol
RIP1 kinase-mediated inflammatory and cell death pathways have been implicated in the pathology of acute and chronic disorders of the nervous system. Here, we describe a novel animal model of RIP1 kinase deficiency, generated by knock-in of the kinase-inactivating RIP1(D138N) mutation in rats. Homozygous RIP1 kinase-dead (KD) rats had normal development, reproduction and did not show any gross phenotypes at baseline. However, cells derived from RIP1 KD rats displayed resistance to necroptotic cell death. In addition, RIP1 KD rats were resistant to TNF-induced systemic shock...
April 7, 2021: Cell Death & Disease