Figure 2. Phenotype and ISG expression in the brain of Adar^P195A/− mice.

(A) Adar^P195A/− mice were produced via breeding of Adar^P195A/P195A mice and heterozygous ADAR1 KO Adar^+/− mice. The ADAR1 KO allele did not produce detectable ADAR1 protein.

(B) Adar^P195A/− mice were viable and healthy; the survival rate of Adar^P195A/− mice was not significantly different from the WT control mice up to 30 weeks of age, as observed in 27 Adar^P195A/− mice.

(C) Expression levels of ISR pathway genes Asns, Cdkn, and Homox in AdarP195A/− mice (n = 5) were not different from the expression levels in the livers of WT controls (n = 5). Cdkn and Homox expression in the brain of Adar^P195A/− mice (n = 5) was increased by less than 2-fold from WT controls (n = 5), while Asns expression was not significantly different. The nonparametric Wilcoxon rank-sum test was used to test the differences between the two groups. *p < 0.05, **p < 0.01.

(D) The body weight of Adar^P195A/− mice was less than that of the controls. In male mice, the body weight showed a statistically significant difference at 4 weeks of age, while the body weight of female mice showed more variation and was statistically different at 2 and 3 weeks of age. n = 5–11 (control male), n = 4–6 (Adar^P195A/P195A male), n = 7–8 (control female), and n = 6–14 (Adar^P195A/P195A female). The nonparametric Wilcoxon rank-sum test was used to test the differences between the two groups. *p < 0.05, **p < 0.01.

(E) The brain ISG expression levels of Adar^P195A/− mice were compared with those of the controls and Adar^P195A/−/Ifih1^−/− mice. All 10 tested ISG mRNA levels were significantly increased in Adar^P195A/− mice, which were significantly decreased in Adar^P195A/−; Ifih1^−/− mice. n = 5 (WT) and n = 6 (Adar^P195A/P195A and Adar^P195A/P195A; Ifih1^−/−). The nonparametric Wilcoxon rank-sum test was used to test the differences between the two groups. **p < 0.01.