'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.
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
P G
PG
Mastroberardino
C
C
Iannicola
R
R
Nardacci
F
F
Bernassola
V
V
De Laurenzi
G
G
Melino
S
S
Moreno
F
F
Pavone
S
S
Oliverio
L
L
Fesus
M
M
Piacentini
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