Loss of Whirlin contributes to abnormal paranodal compaction and cytoskeleton instability throughout sciatic nerve age. A–I. 2-week, 10, 20, 30, 40-week, and 1-yr-old teased sciatic nerve fibers either wild-type (Aa–Ah, Ca–Ch, Ha–Hh) or Whrn knockout (Ba–Bh, Da–Dh, Ea–Eh, Fa–Fh, Ga–Gh, Ia–Ih) immunostained against Kv1.2 (Aa-Ia, red), Caspr (Ab,f–Ib,f, green), NF186 ( Ac-Ic, blue), heavy chain Neurofilament/Nfl-H ( Ae-Ie, red), Protein 4.1 band/4.1B (Ag-Ig, blue), and merged images (Ad,h–Hd,h ). In all Whrn mutant panels, Caspr (Bb,d,f,h; Db,d,f,h; Eb,d,f,h; Fb,d,f,h; Gb,d,f,h, Ib,d,f,h, green) fail to compact properly at the paranodes while juxtaparanodal marker Kv1.2 (Ba,Bd; Da,Dd; Ea,Ed; Fa,Fd; Ga,Gd; Ia,d, red) appears diffuse and disorganized. Nodal NF186 (Ac-Ic, blue) appear unaffected by genotype or age. Cytoskeletal markers like Nfl-H (De-Ge vs. Ce, Ie vs. He, red) and 4.1B (Dg-Gg vs. Cg, Ig vs. Hg, blue) show more diffusion and irregularities in intensity, particularly older animals, in Whrn mutant nerves compared to wild-type nerves, suggesting Whrn contributes to paranodal cytoskeletal stability. Scale bars (Ad-Id, Ah-Ih) = 5 μm. Further quantification and percentages of phenotype-positive sciatic nerves is included for each age/genotype in a summary graph (bottom).