Moreover, synthetic lethality is also observed with Kar3Δ deletion.
Lethality was also observed for the N-terminal truncation and W557S with the muscle-specific drivers Mef2 and how24B, suggesting that the lethality associated with ubiquitous expression was likely due to expression in muscle.
This lethality was also enhanced by heat shock, thus precluding the analysis of the role of p53 in the lethality caused by Mnn1 mis-expression and stress (our unpublished results).
Moreover, lethality was also similar at low challenge dose (60% for wild type KIM D27 and 40% for the single copy dapAX complemented strain) suggesting single copy expression of dapAX is sufficient to restore virulence to near wild type levels (Figure 5A).
The biomass composition, which is very important for flux balance analysis and predicting lethality, was also recalculated and improved.
Lethality was also not correlated with drug susceptibility of Y. pestis isolates, since they were all sensitive to streptomycin, the drug recommended by the national program.
Embryonic lethality was also confirmed in the Fkbpl−/− mice because of the inability to obtain Fkbpl−/− mice with several (>50) intercrosses of Fkbpl+/− mice.
Lethality was also not produced with driver BG57 (Fig. 4A), which expresses in larval muscles from L2 stage and in pupal and adult stages predominantly in abdominal muscle (Supplementary Material, Fig. S5A).
Embryonic lethality was also observed upon deletion of three other components of GQC: Grp78 (Hspa5; which encodes BiP -deleted emBiP -deleted embryoss E3.5 (Luo et al., 2006), Uggt1-null embryos die as early (Molinasi E3.5Luo 2005) and etp57 (Pdial)-null embryos die at E13.5 (Coe et al., 2006).
Severe truncation of peripheral nerve axons and CNS axon tracts in NMNAT2-deficient embryos, likely responsible for their perinatal lethality, is also consistent with a critical axon survival function for NMNAT2 in vivo (Gilley et al., 2013; Hicks et al., 2012).
