Disruption of the lamin-desmin intermediate filament network in lamin A/C–deficient mice. Attachment sites of desmin filaments to the LV cardiomyocyte nuclear surface were identified using immunogold-labeled desmin Ab’s and electron microscopy. Approximately 30 nuclei from WT mice (n = 3), Lmna+/– mice (n = 3), and Lmna–/– mice (n = 3) aged 2 weeks and 4–6 weeks were evaluated. In WT mice (a), desmin filaments (black dots) generally appear as well-defined bands connecting the cytoskeleton with the nuclear surface through nuclear pores (insets). Disorganization of the desmin filaments with detachment from the nuclear surface (with or without widening of the gap between the nuclear and myofibril borders) was observed in 4 (13%) Lmna+/– nuclei (b) and 16 (59%) Lmna–/– nuclei (d), but in none of the WT nuclei at 4–6 weeks. These changes were evident in 14 (50%) Lmna–/– nuclei (c) at 2 weeks; scale bar = 0.25 μm. Immunostaining with a desmin Ab (e–h) shows normal Z disc striations and intercalated discs in WT and Lmna+/– mice, but progressive disorganization of the desmin filament network in 2-week-old (g) and 4- to 6-week-old (h) Lmna–/– mice. Scale bar: 5 μm.