Figure 4.

In vivo phenotype characterization of mice repopulated with unedited and edited OTCD or OTCP hepatocytes

(A) Basal blood ammonia levels in humanized mice. Unedited OTCD mice n = 9. Edited OTCD mice n = 18. OTCP mice n = 17. Unedited OTCD versus edited OTCD, p = 0.0018; unedited OTCD versus OTCP, p = 0.0004; edited OTCD versus OTCP, p > 0.9999. (B) Blood ammonia levels in humanized mice measured 30 min post-injection of ¹⁵NH₄Cl (ammonia challenge). Unedited OTCD mice n = 9. Edited OTCD mice n = 18. OTCP mice n = 17. Unedited OTCD versus edited OTCD, p = 0.0003; unedited OTCD versus OTCP, p < 0.0001; edited OTCD versus OTCP, p = 0.0041. (C) Urinary orotic acid in humanized mice normalized to urinary creatinine. Unedited OTCD mice n = 9. Edited OTCD mice n = 15. OTCP mice n = 16. Unedited OTCD versus edited OTCD, p = 0.0158; unedited OTCD versus OTCP, p < 0.0001; edited OTCD versus OTCP, p = 0.0268. (D) OTC enzyme activity in humanized mouse livers. Unedited OTCD mice n = 9. Edited OTCD mice n = 10. OTCP mice n = 10. Unedited OTCD versus edited OTCD, p = 0.0112; unedited OTCD versus OTCP, p < 0.0001; edited OTCD versus OTCP, p = 0.3452. (E) CPS1 enzyme activity in humanized mouse livers. Unedited OTCD mice n = 9. Edited OTCD mice n = 10. OTCP n = 10. Unedited OTCD versus edited OTCD, p = 0.2486; unedited OTCD versus OTCP, p = 0.1743; edited OTCD versus OTCP, p = 0.9745. Averages and errors are shown as medians and interquartile ranges. Kruskal-Wallis ANOVA and Dunn’s multiple comparison tests were used to perform statistical analysis for datasets not normally distributed (basal ammonia, urinary orotic acid, and OTC enzyme assay), while ordinary ANOVA and Tukey multiple comparison tests for datasets normally distributed (post-injection ammonia and CPS1 enzyme activity).