Table 1.
Characteristics of the mouse lines used in the present study.
Table 2.
Summary table of the primary antibodies used in the present study.
Fig 1.
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).
Fig 2.
High power light microscopy images of mHTT antibody staining of striatal aggregation pathology in early disease HD mice.
The R6/1 mice demonstrated NIIs with all antibodies (A,F,K,P,U), whereas the YAC128 mice demonstrate no NIIs but faint diffuse staining with all antibodies (G,L,Q,V) except S830 (B). The antibodies also failed to detect NIIs in the HdhQ92 line at this age (Photomicrographs C,H,M,R,W) but did demonstrate diffuse staining with all. Both HdhQ150 lines were insensitive to EM48 (N,O) with the original HdhQ150 line also being insensitive to 1C2 (X), but the Photomicrographs for S830 (D), MW8 (I) and ubiquitin (X) in the original line demonstrated good sensitivity for NIIs, as they did for the B6 variant (Photomicrographs E,J, Y respectively). Scale bar = 10 μm.
Fig 3.
High power light microscopy images of mHTT antibody staining of striatal aggregation pathology in later disease HD mice.
The R6/1, YAC128 and HdhQ92 mice were sensitive to each of the antibodies (R6/1 Photomicrographs A,F,K,P,U; YAC128 Photomicrographs B,G,L,Q,V; HdhQ92 Photomicrographs C,H,M,R,W), whereas both HdhQ150 lines where sensitive to all but EM48 (B6 HdhQ150 Photomicrographs E,J,O,T,Y; original HdhQ150 Photomicrographs D,I,N,S,X). Scale bar = 10 μm.
Table 3.
Means and standard errors of the data sets used in the present study.
(See S1 File for raw data).