Dysregulation of Temperature and Liver Cytokine Gene Expression in Immunodeficient Wasted Mice

Wasted mice bear the spontaneous autosomal recessive mutationwst/wst;this genotype is associated with weight loss beginning at 21 days of age, neurologic dysfunction, immunodeficiency at mucosal sites, and increased sensitivity to the killing effects of ionizing radiation. The pathology underlying the disease symptoms is unknown. Experiments reported here were designed to examine thermoregulation and liver expression of specific cytokines in wasted mice and in littermate and parental controls. Our experiments found that wasted mice begin to show a drop in body temperature at 21–23 days following birth, continuing until death at the age of 28 days. Concomitant with that, livers from wasted mice expressed increased amounts of mRNAs specific for cytokines IL-6 and IL-1, the acute phase reactant C-reactive protein, c-jun,and apoptosis-associated Rp-8 when compared to littermate and parental control animals. Levels of β-transforming growth factor, c-fos,proliferating cell nuclear antigen, and ornithine amino transferase transcripts were the same in livers from wasted mice and controls. These results suggest a relationship between an acute phase reactant response in wasted mice and temperature dysregulation.