Partial TG6 loss of function causes motor deficits in male mice

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

Abstract Mutations in Transglutaminase 6 (TG6) have been linked to a genetic form of spinocerebellar ataxia, namely SCA35. In recent years, several mutations associated with this disease have been identified. While some of them did not alter TG6 enzymatic activity, others induced a dominant-negative loss-of-function and altered subcellular localization. We previously observed that mutations identified in patients, which showed detrimental effects on neuronal viability in vitro, including mislocalization and activation of the unfolded protein response, were consistently characterized by a loss of TG6 enzymatic function. To investigate this effect, we re-derivedknockout mice from the EMMA repository and performed behavioral characterization. We measured body weight and assessed motor performance using the rotarod, elevated beam/beam balance test, and ladder test, beginning at 1 month of age and continuing through 16 months of age. Here, we report that TG6 loss-of-function impairs motor coordination in male mice, suggesting a sex-specific function for this enzyme.