Female mice with an ancestral history of Khdc3 mutation manifest hepatic transcriptional dysregulation that is independent of genotype.
(a) Gene ontology scatterplot for dysregulated genes in Khdc3-null oocytes, based on RNA-Seq. The y-axis represents −log FDR (false discovery rate) and the x-axis represents log2 enrichment ratio. Dysregulation of genes important in lipid and carbohydrate metabolism are highlighted. (b) Murine expression of Khdc3 in various tissues, detected by qPCR (N=3). (c) Relative mRNA expression of Cyp17a1 in the livers of WT, WT*, KOKO, and KO* mice measured by qPCR. Each dot represents an individual mouse. (d) Relative mRNA expression of Cyp17a1 in the livers of WT* female mice generated from various male and female Khdc3-null grandparents measured by qPCR. (e) Volcano plots depicting differentially expressed genes identified by RNA-seq in the livers of WT vs. WT*, KO* and KOKO mice, respectively (N=4-6). Red dots represent upregulated genes in WT*, KO* and KOKO mice while blue dots represent genes that were downregulated in WT*, KO* and KOKO mice. The x-axis shows log2 fold change values, and the y-axis denotes −log10 p-values. (f) Dot plots of common dysregulated liver genes amongst the WT*, KO*, and KOKO mice compared to WT mice; ***p-adjusted < 1 x 10-5. (g) Dot plot of the significantly dysregulated genes in KO* livers (x-axis) versus WT* livers (y-axis), based on adjusted p-value. Red dots reveal significantly dysregulated genes in KO* mice, blue dots reveal significantly dysregulated genes in WT* mice, and grey dots represent commonly significantly dysregulated genes in both KO* and WT* mice. (h) Gene ontology of the most common dysregulated genes identified in the livers of both WT* and KO* revealed abnormalities in pathways critical for lipid and glucose metabolism.