Transgenic models to assess the pathogenic actions of cytokines in the central nervous system.
In order to better understand the actions of proinflammatory cytokines in the mammalian CNS, a transgenic approach was employed in which the expression of IL-6, IL-3 or TNF-alpha was targeted to astrocytes in the intact CNS of mice. Transgenic mice exhibited distinct chronic-progressive neurological disorders with neurodegeneration and cognitive decline due to IL-6 expression, macrophage/microglial-mediated primary demyelination with motor impairment due to IL-3 expression and lymphocytic meningoencephalomyelitis with paralysis induced by TNF-alpha expression. Thus, expression of specific cytokines alone in the intact CNS results in unique neuropathological alterations and functional impairments, thereby directly implicating these mediators in the pathogenesis of CNS disease.
Campbell
I L
IL
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA. icamp@scripps.edu
Stalder
A K
AK
Chiang
C S
CS
Bellinger
R
R
Heyser
C J
CJ
Steffensen
S
S
Masliah
E
E
Powell
H C
HC
Gold
L H
LH
Henriksen
S J
SJ
Siggins
G R
GR
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002493:Central Nervous System Diseases / Q000503:physiopathology*; D003072:Cognition Disorders / Q000503:physiopathology; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D003711:Demyelinating Diseases / Q000503:physiopathology; D004679:Encephalomyelitis / Q000503:physiopathology; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D007377:Interleukin-3 / Q000235:genetics / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology; D008590:Meningoencephalitis / Q000503:physiopathology; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009069:Movement Disorders / Q000503:physiopathology; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology
D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D007377:Interleukin-3; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha