J Clin Invest.
Suppressing mutant TDP-43 expression results in partial recovery of motor function in rats.
(A) Immunoblotting revealed that Dox treatment (Dox+) suppressed the expression of mutant TDP-43 transgene (hTDP-43) as early as 5 days after Dox was administered. Equal loading was probed with an antibody to GAPDH. Tissues: FB, forebrain; SM, skeletal muscle. (B–D) Representative photographs show a M337V rat at paralysis stage (B) and at 10 days (C) and 2 months (D) after Dox treatment. (E) Open-field assay revealed a quick recovery of mobility in M337V rats after the transgene was turned off by Dox treatment (Dox+). (F) The grip strength of hind paws was partially recovered in M337V rats after the transgene was turned off. NEF-tTA denotes NEF-tTA single-transgenic rats, and M337V denotes NEF-tTA/TRE–TDP-43M337V double-transgenic rats. Data are means ± SD (n = 7).