Metallothionein-1+2 deficiency increases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin 6

Mercedes Giralt, Milena Penkowa, Joaquín Hernández, Amalia Molinero, Javier Carrasco, Natalia Lago, Jordi Camats, Iain L. Campbell, Juan Hidalgo*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículoInvestigaciónrevisión exhaustiva

60 Citas (Scopus)

Resumen

Transgenic expression of IL-6 under the control of the GFAP gene promoter (GFAP-IL6 mice) in the CNS causes significant damage and alters the expression of many genes, including the metallothionein (MT) family, especially in the cerebellum. The crossing of GFAP-IL6 mice with MT-1+2 knock out (MTKO) mice provided evidence that the increased MT-1+2 expression normally observed in the GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, the GFAP-IL6xMTKO mice showed a decreased body weight gain and an impaired performance in the rota-rod test, as well as a higher upregulation of cytokines such as IL-6, IL-1α,β, and TNFα and recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. Clear symptoms of increased oxidative stress and apoptotic cell death caused by MT-1+2 deficiency were observed in the GFAP-IL6xMTKO mice. Interestingly, MT-1+2 deficiency also altered the expected frequency of the offspring genotypes, suggesting a role of these proteins during development. Overall, the results suggest that the MT-1+2 proteins are valuable factors against cytokine-induced CNS injury. © 2002 Elsevier Science (USA).
Idioma originalInglés
Páginas (desde-hasta)319-338
PublicaciónNeurobiology of Disease
Volumen9
DOI
EstadoPublicada - 1 ene 2002

Huella

Profundice en los temas de investigación de 'Metallothionein-1+2 deficiency increases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin 6'. En conjunto forman una huella única.

Citar esto