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*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

57 Citations (Scopus)

Abstract

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).
Original languageEnglish
Pages (from-to)319-338
JournalNeurobiology of Disease
Volume9
DOIs
Publication statusPublished - 1 Jan 2002

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