LAMB2 and Hirschsprung disease: In parallel to the defective innervation of the hindgut causing distal aganglionosis, Edn3ls/ls mutant mice also exhibited upregulation of ECM components (laminins (α1, β1, and γ1) and collagens IV) in the non-neuronal mesenchymal cells of the fetal colon, resembling the ECM abnormalities reported in HSCR patients (see details in Section 3.1).