Mice homozygous for the Il1r1tm1Roml targeted mutation develop normally, exhibit a reduced inflammatory response and no response to interleukin-1 alpha or beta. Homozygous mice have a reduced acute phase and delayed type hypersensitivity response and are highly susceptible to Listeria monocytogenes infection. Equilibrium binding experiments using radiolabeled anti-mouse IL1R1 antibody, 35F5, show no detectable expression of IL1R1 protein in primary murine embryonic fibroblasts (Labow et al, 1997). NOD females homozygous for the Il1r1tm1Roml mutation experience a slight, yet significant delay in diabetes development, with an overall incidence of 75% compared to 100% in wild types. There is no statistical difference between mutant and wild type NOD mice in diabetes development following cyclophosphamide treatment or in the rate at which they mediate autoimmune rejection of syngeneic fetal pancreatic grafts. Adoptive transfer of NOD.Cg-Tg(TcraBDC2.5)1DoiTg(TcrbBDC2.5)2Doi Prkdc scid spleen cells results in diabetes onset in irradiated NOD.Cg-Il1r1tm1Roml recipients at 20 days post-transfer, compared to 11 days in wild type recipients. Introduction of the Il1r1tm1Roml mutation does not alter the rate of diabetes development in NOD.Cg-Tg(8.3TCR) mice (Thomaset al, 2004). Islets isolated from Il1r1 homozygous mice are resistant to toxic effects of cytokines.
This mutant mouse strain may be useful in studies of the role of interleukin-1receptor type 1 in autoimmune diseases such as type 1 diabetes.
