title: Loss of glial fibrillary acidic protein marginally accelerates disease progression in a SOD1(H46R) transgenic mouse model of ALS.
abstract: Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is highly expressed in reactive astrocytes. Increased production of GFAP is a hallmark of astrogliosis in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). However, the physiological and pathological roles of GFAP, particularly in chronic neurodegenerative conditions, remain unclear. To address this issue, we here investigate whether absence of GFAP affects the phenotypic expression of motor neuron disease (MND) using an H46R mutant Cu/Zn superoxide dismutase-expressing mouse model of ALS (SOD1(H46R)). GFAP deficient SOD1(H46R) mice showed a significant shorter lifespan than SOD1(H46R) littermates. Further, at the end stage of disease, loss of GFAP resulted in increased levels of Vim and Aif1 mRNAs, encoding vimentin and allograft inflammatory factor 1 (AIF1), respectively, in the spinal cord, although no discernible differences in the levels and distribution of these proteins between SOD1(H46R) and GFAP-deficient SOD1(H46R) mice were observed. These results suggest that loss of GFAP in SOD1(H46R) mice marginally accelerates the disease progression by moderately enhancing glial cell activation. Our findings in a mouse model of ALS may have implication that GFAP is not necessary for the initiation of disease, but it rather plays some modulatory roles in the progression of ALS/MND.
authors: Department of Neurology, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143-8541, Japan.
authors: Yasuhiro
authors: Y
authors: Yoshii
authors: Asako
authors: A
authors: Otomo
authors: Lei
authors: L
authors: Pan
authors: Masato
authors: M
authors: Ohtsuka
authors: Shinji
authors: S
authors: Hadano
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D005904:Glial Fibrillary Acidic Protein; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1