Genetic analysis of extrathyroidal features of Obese strain (0s) chickens with spontaneous autoimmune thyroiditis*
The Obese strain (0s) of chickens, which is afflicted with Hashimoto-like spontaneous autoimmune thyroiditis (SAT), displays elevated T cell proliferation, interleukin (IL) 2 production and IL2 receptor expression upon mitogen stimulation, and defects in the neuroendocrine control of the immune system including elevated corticosteroid-binding globulin (CBG) and a deficient increase of serum corticosterone (CN) upon cytokine injection. Recently this strain has further been shown to harbor retrovirus-related sequences (endogenous virus no. 22, ev22) absent in healthy control strains. To determine the number of genes responsible for SAT-associated immunodysregulation and to unravel possible ev22 associations, we analyzed the above immune and endocrine parameters in F1 h brids and backcrosses of the autoim-OS-like T cell hyperproliferation and IL 2 hypersecretion in response to both concanavalin A and phytohemagglutinin were transmitted as autosomal dominant traits and co-segregated in backcross animals. In vivo hyporesponse of the 0s to the corticosterone-inducing effect of cytokine preparations was inherited dominantly and the elevated CBG serum levels recessively. None of these traits appeared to be major histocompatibility complex (MHC) linked. However, while T cell abnormalities and elevated CBG serum levels were not associated with the autosomal ev22 locus, in vivo hyporesponsiveness to glucocortocoid-inducing cytokines co-segregated with this OSspecific provirus. These results add to the concept of SAT as a polyetiological and plurigenetic disease and do not support our previous hypothesis that T cell hyperreactivity and immunoendocrine dysfunction might be functionally related. mune 0s B15B'S with healthy inbred CB B12B' Y .
chickens.