Figure 2.

The ISR is a conserved gene signature in the livers of juvenile and adult mice following 1 week of daily ASNase exposure. A, Venn diagram representing functional annotations of the common and unique gene signatures in juveniles (2 weeks old) and adults (8 and 16 weeks old) exposed to ASNase daily for 1 week. B, the shared or common transcriptional signature in liver following chronic ASNase exposure includes the activating transcription factor 4 (ATF4) target genes Fgf21, Trib3, Asns, Nupr1, Exlt1, Atf5, and other genes from Table S1A. Data are represented as means normalized to the juvenile (Juv) PBS control group ± S.D. (error bars); means not sharing a common letter are significantly different, padj < 0.1. C, transcript levels of Fgf21 and Trib3 in the livers of juvenile and adult mice were confirmed by RT-qPCR. D, immunoblot analysis of phosphorylation of eIF2 α-subunit at serine 51 (p-S51-eIF2) substantiates similar ISR induction to ASNase across ages. Lamin B1, but not eIF2 or β-tubulin, decreases with age. Densitometry of blots are shown to the right of the representative immunoblots. Bar graphs display means normalized to the juvenile (Juv) PBS control group ± S.D. Data displayed in C and D were evaluated by Wilcoxon rank-sum test. *, p < 0.05. n.s., not significant.