RNA-seq analysis of E18.5 mouse embryonic lungs reveals impaired saccular maturation and airway differentiation in Svep1 knockout embryos

Loss of Svep1, an extracellular matrix protein, leads to severe defects in airway patterning and alveolar differentiation during lung development. To investigate transcriptional changes associated with impaired saccular maturation, we performed bulk RNA sequencing of whole lungs isolated from wild-type (Svep1+/+) and homozygous knockout (Svep1-/-) mouse embryos at embryonic day 18.5 (E18.5), corresponding to the saccular stage of lung development. Differential gene expression analysis revealed dysregulation of pathways related to extracellular matrix organization, smooth muscle differentiation, epithelial maturation, and FGF signaling. These data provide insight into how loss of Svep1 disrupts coordinated epithelial–mesenchymal interactions required for normal distal lung development. Overall design: Whole lungs were dissected from E18.5 mouse embryos generated from heterozygous Svep1 intercrosses. Genotypes were determined by PCR and embryos were grouped as wild-type (Svep1+/+) or knockout (Svep1-/-). Total RNA was extracted from individual whole lungs. Poly(A)-selected RNA-seq libraries were prepared and sequenced on an Illumina platform. Differential gene expression analysis was performed comparing Svep1-/- versus Svep1+/+ lungs.