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. Author manuscript; available in PMC: 2022 May 19.
Published in final edited form as: Sci Transl Med. 2022 Jan 19;14(628):eabi9196. doi: 10.1126/scitranslmed.abi9196

Fig. 1. Cryptic exon detection is a sensitive and specific assay for TDP-43 pathology in IBM biopsies.

Fig. 1.

(A) TDP-43 Western blot in myoblasts treated with TDP43 siRNA [knockdown (KD)] compared to control siRNA (C). (B) Visualization of cryptic exons (green arrows) in myoblast cells with TDP-43 knockdown (MyoKD) compared to control (MyoC) for TDP-43 target genes ACOT11, SLC39A8, PFKP, and RHEBL1. ACOT11, acyl-CoA thioesterase 11; SLC39A8, solute carrier family 39 member 8; PFKP, phosphofructokinase, platelet; RHEBL1, RHEB (ras homolog, mechanistic target of rapamycin kinase binding) like 1. (C) Immunohistochemical TDP-43 staining of muscle sections showing accumulation of TDP-43 in the cytoplasm (#) or nuclear clearing (arrows). Scale bar, 50 μm. (D) Visualization of cryptic exons (green arrow) in control myoblasts (MyoC), myoblasts with TDP-43 knockdown (MyoKD), or subject muscle biopsies [control (C) and IBM]; numbers indicate cases (table S2). (E) Representative gel showing cryptic exon expression from TDP-43 target genes GPSM2, ACSF2, HDGFRP2, and ZFP91 in skeletal muscle biopsies from IBM and control biopsies (DM, dermatomyositis; NA, neurogenic atrophy; C, normal muscle or mild nonspecific features).