Abstract
By crossing Huntington's disease (HD) R6/1 transgenic mice with ‘tissue’ transglutaminase (TG2) knock-out mice, we have demonstrated that this multifunctional enzyme plays an important role in the neuronal death characterising this disorder in vivo. In fact, a large reduction in cell death is observed in R6/1, TG2−/− compared with R6/1 transgenic mice. In addition, we have shown that the formation of neuronal intranuclear inclusions (NII) is potentiated in absence of the ‘tissue’ transglutaminase. These phenomena are paralleled by a significant improvement both in motor performances and survival of R6/1, TG2−/− versus R6/1 mice. Taken together these findings suggest an important role for tissue transglutaminase in the regulation of neuronal cell death occurring in Huntington's disease.
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Abbreviations
- HD:
-
Huntington's disease
- NII:
-
neuronal intranuclear inclusions
- TG2:
-
type 2 transglutaminase
- htt:
-
huntingtin
- ANOVA:
-
analysis of variance between groups
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Acknowledgements
The authors would like to express their gratitude to Professors F Autuori and A Ciofi-Luzzatto for stimulating discussions, Dr. Enrico Girardi for the statistical analysis, Valentina Imbroglini for technical assistance and Dr. G Citro from Istituto Regina Elena, Rome, Italy for animal care and stabulation. The work was partially supported by grants from: European Community ‘Apoptosis Mechanisms’, AIRC. The financial support of Telethon-Italy (Grant n. E.1257 to F Bernassola) is gratefully acknowledged.
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Mastroberardino, P., Iannicola, C., Nardacci, R. et al. ‘Tissue’ transglutaminase ablation reduces neuronal death and prolongs survival in a mouse model of Huntington's disease. Cell Death Differ 9, 873–880 (2002). https://doi.org/10.1038/sj.cdd.4401093
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DOI: https://doi.org/10.1038/sj.cdd.4401093
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