Figure 4.

Loss of klhl41 Function in Zebrafish Recapitulates the Disease Pathology of Human Nemaline Myopathies

(A) Whole-mount staining of 3 dpf zebrafish embryos with phalloidin showed extensive myofibrillar disarray of myofibers in klhl41 morphant fish (scale bar represents 2 μm). Three dpf embryos fixed in 4% paraformaldehyde were incubated with phalloidin (Invitrogen, A12380, 1:40) overnight at 4°C. Skeletal muscles of klhl41-deficient embryos were smaller and exhibited an overall reduction of myofibrillar organization (inset, high magnification).

(B) Electron microscopy of klhl41-deficient skeletal muscle revealed thickened Z-lines in klhl41a or klhl41b morphants. In addition, skeletal muscle of double knockdown fish contained electron dense bodies, reminiscent of nascent nemaline rods (arrowhead, nemaline bodies like structures; arrow, thickened Z-lines) (scale bar represents 1 μm).