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Partial TG6 loss of function causes motor deficits in male mice
Luisa Donini1, Linda Sartori1, Anna Barbieri1
1Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, via Sommarive 9, 38123 Trento, Italy.
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 in vivo, we re-derived Tgm6 knockout 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.
Insights
Transglutaminase 6 (TG6) loss-of-function impairs motor coordination in male mice. This suggests a sex-specific role for TG6 in maintaining neurological function and motor control.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Mutations in Transglutaminase 6 (TG6) are linked to spinocerebellar ataxia type 35 (SCA35).
- Some TG6 mutations cause loss-of-function and altered cellular localization, impacting neuronal viability.
- Previous in vitro studies showed TG6 loss-of-function correlates with detrimental effects on neurons.
Purpose of the Study:
- To investigate the in vivo effects of TG6 loss-of-function on motor performance.
- To characterize the behavioral phenotype of Tgm6 knockout mice.
- To explore potential sex-specific roles of TG6 in motor control.
Main Methods:
- Re-derived Tgm6 knockout mice from the EMMA repository.
- Conducted behavioral characterization from 1 to 16 months of age.
- Assessed motor performance using rotarod, elevated beam/beam balance, and ladder tests; measured body weight.
Main Results:
- TG6 loss-of-function significantly impairs motor coordination in male mice.
- No specific mention of female mouse performance or body weight changes in the abstract.
- The observed motor deficits suggest a role for TG6 in motor control.
Conclusions:
- TG6 loss-of-function leads to impaired motor coordination in male mice.
- These findings suggest a sex-specific function for Transglutaminase 6 in the nervous system.
- Further research is warranted to elucidate the precise mechanisms and implications of TG6's sex-specific role.
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