Correction: Further investigation of phenotypes and confounding factors of progressive ratio performance and feeding behavior in the BACHD rat model of Huntington disease.

[This corrects the article DOI: 10.1371/journal.pone.0173232.].

Dynamic nuclear envelope phenotype in rats overexpressing mutated human torsinA protein.

A three-base-pair deletion in the human TOR1A gene is causative for the most common form of primary dystonia: the early-onset dystonia type 1 (DYT1 dystonia). The pathophysiological consequences of this mutation are still unknown. To study the pathology of the mutant torsinA (TOR1A) protein, we have generated a transgenic rat line that overexpresses the human mutant protein under the control of the human TOR1A promoter. This new animal model was phenotyped with several approaches, including behavioral tests and neuropathological analyses. Motor phenotype, cellular and ultrastructural key features of torsinA pathology were found in this new transgenic rat line, supporting that it can be used as a model system for investigating the disease's development. Analyses of mutant TOR1A protein expression in various brain regions also showed a dynamic expression pattern and a reversible nuclear envelope pathology. These findings suggest the differential vulnerabilities of distinct neuronal subpopulations. Furthermore, the reversibility of the nuclear envelope pathology might be a therapeutic target to treat the disease.

Further investigation of phenotypes and confounding factors of progressive ratio performance and feeding behavior in the BACHD rat model of Huntington disease.

Huntington disease is an inherited neurodegenerative disorder characterized by motor, cognitive, psychiatric and metabolic symptoms. We recently published a study describing that the BACHD rat model of HD shows an obesity phenotype, which might affect their motivation to perform food-based behavioral tests. Further, we argued that using a food restriction protocol based on matching BACHD and wild type rats' food consumption rates might resolve these motivational differences. In the current study, we followed up on these ideas in a longitudinal study of the rats' performance in a progressive ratio test. We also investigated the phenotype of reduced food consumption rate, which is typically seen in food-restricted BACHD rats, in greater detail. In line with our previous study, the BACHD rats were less motivated to perform the progressive ratio test compared to their wild type littermates, although the phenotype was no longer present when the rats' food consumption rates had been matched. However, video analysis of food consumption tests suggested that the reduced consumption rate found in the BACHD rats was not entirely based on differences in hunger, but likely involved motoric impairments. Thus, restriction protocols based on food consumption rates are not appropriate when working with BACHD rats. As an alternative, we suggest that studies where BACHD rats are used should investigate how the readouts of interest are affected by motivational differences, and use appropriate control tests to avoid misleading results. In addition, we show that BACHD rats display distinct behavioral changes in their progressive ratio performance, which might be indicative of striatal dysfunction.