Post-mitotic Neuronal Apoptosis and Perinatal Lethality with Loss of Setd2/H3K36me3
(A) (i) Asynchronous and (ii) STI-571 G1-arrested WT, Xrcc5, and two different Setd2−/− v-Abl cells subjected to different doses of ionizing radiation and serially diluted five times in triplicate to assess survival. Values plotted as a mean of each dose as a percent of non-irradiated controls; bars represent standard deviation. Data are representative for three different independent treatment experiments. Viability was assessed at 72 h. No viable cells were detected beyond the 0.5 Gy dose for G1-arrested Xrcc5 v-Abl clones.
(B) Expected and observed genotype distributions of matings between Nestin-cre Setd2Δ/+ mice to Setd2f/+ mice (n = 15 litters) and Nestin-cre Setd2Δ/+ mice to Setd2f/f mice (n = 16 litters) 21 days post-partum (dpp).
(C) Embryo genotypes at different embryonic stages (n = 5 litters for each stage).
(D) Litter sizes of E14.5, E16.5, E18.5, and 0.25 dpp from Nestin-cre Setd2Δ/+ mice to Setd2f/f breedings. Significance to 0.25 dpp was measured (n = 5 litters for each stage except 0.25 dpp, n = 11).
(E) Cleaved caspase 3 immunohistochemistry of E18.5 embryos. Sagittal sections show staining of regions of the diencephalic, telencephalic, and mesencephalic regions with magnifications indicated by corresponding colored boxes.
(F) TUNEL assay of 2-h post-partum control and Nestin-cre Setd2Δ/Δ pups. Coronal sections of the lateral ventricle with magnifications indicated by corresponding red and green boxes.
∗∗p < 0.01 ∗∗∗p < 0.001, error bars represent SD. See also Figures S10 and S11.