'Tissue' transglutaminase ablation reduces neuronal death and prolongs survival in a mouse model of Huntington's disease.
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.
Mastroberardino
P G
PG
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Iannicola
C
C
Nardacci
R
R
Bernassola
F
F
De Laurenzi
V
V
Melino
G
G
Moreno
S
S
Pavone
F
F
Oliverio
S
S
Fesus
L
L
Piacentini
M
M
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D016923:Cell Death / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D019204:GTP-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D006160:Guanosine Triphosphate / Q000378:metabolism; D006816:Huntington Disease / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009043:Motor Activity / Q000235:genetics; D019579:Neocortex / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D017072:Neostriatum / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015996:Survival Rate; D011503:Transglutaminases / Q000172:deficiency* / Q000235:genetics
D009419:Nerve Tissue Proteins; D006160:Guanosine Triphosphate; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins