Mastroberardino P G, Iannicola C, Nardacci R, Bernassola F, De Laurenzi V, Melino G, Moreno S, Pavone F, Oliverio S, Fesus L, Piacentini M
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Cell Death Differ. 2002 Sep;9(9):873-80. doi: 10.1038/sj.cdd.4401093.
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.
通过将亨廷顿舞蹈症（HD）R6/1转基因小鼠与“组织”转谷氨酰胺酶（TG2）基因敲除小鼠杂交，我们已经证明这种多功能酶在该疾病体内特征性的神经元死亡中起重要作用。事实上，与R6/1转基因小鼠相比，在R6/1、TG2（-/-）小鼠中观察到细胞死亡大幅减少。此外，我们已经表明，在没有“组织”转谷氨酰胺酶的情况下，神经元核内包涵体（NII）的形成会增强。这些现象与R6/1、TG2（-/-）小鼠相对于R6/1小鼠在运动性能和存活率方面的显著改善同时出现。综合这些发现表明，组织转谷氨酰胺酶在亨廷顿舞蹈症中发生的神经元细胞死亡调节中起重要作用。
