Phenotype of Rnaseh2b^KOF mice with low levels of residual RNase H2 activity. (A) Control and stillborn homozygous Rnaseh2b^KOF/KOF neonate. (B) Neonates from heterozygous (Rnaseh2b^KOF/WT) breedings. *, all homozygous neonates were dead upon first inspection. (C) E14.5 embryos from heterozygous (Rnaseh2b^KOF/WT) breedings. (D) Histology of E14.5 Rnaseh2b^KOF/KOF embryos and littermate controls. Left and middle, H&E-stained section of E14.5 Rnaseh2b^KOF/KOF and control skin. Note massive edema in mutant skin. Right, H&E-stained section of E14.5 Rnaseh2b^KOF/KOF tongue. Note the extravasated erythrocytes (arrow) in the muscle tissue. Similar bleedings were detected in numerous tissues of most embryos. (E) Quantification of WT RNaseh2b transcripts in fibroblasts from Rnaseh2b^KOF/KOF and control E14.5 embryos. Mean ± SD of three pairwise comparisons are displayed. (F) RNase H2 activity in E14.5 fibroblasts. Cleavage of an 18-bp dsDNA substrate containing a single ribonucleotide was measured and activity was calculated from the slope of the graphs (means, represented as percentage of WT).