Whirlin alone and combination 4.1B/Whirlin knockout mice have cerebellar Purkinje cells with bead-like, axonal swellings. A–D. 6-week sagittal sections of mouse cerebellum in either wild-type (Aa–Af), Whrn knockout (Ba–Bf), or double Whrn knockout and 4.1B null (Ca–Cf, Da–Df) immunostained against Protein 4.1B band/4.1B (Aa–Da, Ad–Dd, red), Calbindin (Ab–Db, green), myelin basic protein/MBP vAe–De, green), and merged images (Ac,f–Dc,f). No striking difference was observed between wild-type and Whrn knockout slices in 4.1B staining (Aa,d vs. Ba,d) and only non-specific staining was present in 4.1B null animals (Ca–Da, Cd–Dd). In Whrn mutant cerebellum sections (Ba–Bf), Purkinje axonal swellings appear bead-like using both Calb (Bb,c vs. Ab,c) and MBP (Be,f vs. Ae,f) in comparison to a uniform, thin caliber axon in wild-type fibers (Aa–f). Additionally, secondary ablation of 4.1B protein resulted in a greater number of swellings observed with Calb (Cb,c–Db,c vs. Bb,c) and MBP (Ce,f–De,f vs. Be,f) when compared with Whrn knockouts alone suggesting these cytoskeletal elements help prevent cytoskeletal disorganization in Purkinje cell axons. Scale bars (Ac–Dc, Af–Df) = 10 μm.