Ataxin-1 oligomers induce local spread of pathology and decreasing them by passive immunization slows Spinocerebellar ataxia type 1 phenotypes
- Baylor College of Medicine, United States
- Texas Children's Hospital, United States
- University of Texas Medical Branch, United States
- Howard Hughes Medical Institute, Baylor College of Medicine, United States
- University of Minnesota, United States
- Baylor College of Medicine, United states
Figures
Figure 1 with 2 supplements
ATXN1 oligomers propagate further ATXN1 oligomerization in vivo.
(A) Representative western blot brain lysates used for in vivo injections. F11G3 was used to detect oligomers (WT and Atxn1154Q/+, cerebellar samples). (B) Table of mouse genotypes and treatments …
Figure 1—figure supplement 1
Anti-oligomer antibody F11G3 blocks the formation of oligomers in cells treated with ATXN1 oligomers from Atxn1154Q/+mouse cerebellum.
Quantification of the percentage of mRFP-ATXN1(82Q) cells with oligomeric (blue bars) or fibrillar (red bars) inclusions following treatment of Atxn1154Q/+or WT mouse cerebellum alone or …
Figure 1—figure supplement 2
Oligomer propagation is accompanied by slight motor deficit in Atxn178Q/+ mice.
Rotarod assay over a four-day period (four trials per day, averaged), 3 months following lysate injection. n = 8 per genotype. ** denotes p<0.01, ANOVA followed by Bonferroni’s post hoc test.
Figure 2 with 1 supplement
Anti-oligomer immunotherapy decreases pathology in vivo.
(A) Histological staining of PCs (Calbindin, top panels) and Oligomers (A11, bottom panel) of control (IgM) and treated (F11G3) Atxn1154Q/+ mice. Adjacent sections were used for comparison. (B) …
Figure 2—figure supplement 1
Oligomers are detected in Atxn1154Q/+ cerebellum at four weeks of age.
Western blot against F11G3 to detect oligomers in cerebella from four (lanes 1 and 2) and 11 week (panels 3 and 4) old WT and Atxn1154Q/+ mice. Oligomers are detected in Atxn1154Q/+ at four weeks, …
Figure 3
Anti-oligomer immunotherapy improves motor deficits and survival in vivo.
(A–B) Western blot detecting ATXN1 oligomers (F11G3, top panel) and ATXN1 monomer (11750, middle panel) in the cerebellum of Atxn1154Q/+following immunotherapy (anti-oligomer or control). * in (A) …
