mHTT antibody binding in young and old animals from 5 HD mouse models.
R6/1 mice demonstrate some diffuse staining (A) but high levels of frank inclusions from 4 months of age (B). In this mouse line EM48 was overall the most sensitive antibody, with 1C2 and ubiquitin the least. In young YAC128 mice that demonstrate only diffuse staining (C,D), ubiquitin and S830 were the most effective antibodies. As the mice aged MW8 became the most sensitive antibody. In the HdhQ92 mice, EM48 was the most effective antibody in the young animals (E) with S830 the most effective in the old (F) where the other four antibodies demonstrated a consistent level of mHTT detection. For the HdhQ150 strains, both lines were insensitive to EM48 and demonstrated relatively little binding of diffuse staining per se (original line G,H; B6 backcross I,J) with the antibodies detecting inclusions at high levels even at a young age. The original HdhQ150 line demonstrated consistent levels of detection with the four usable antibodies including 1C2, which was ineffective in the B6 line. MW8 was the most sensitive antibody in the B6 line. Significance markers omitted for clarity (See S1 File for raw data).