Upregulation of metallothionein-I mRNA expression in a rodent model for amyotrophic lateral sclerosis.
Metallothionein (MT) mRNA expression was investigated in a rodent model (G93A SOD1 transgenic mouse) for a lethal motor neuron disease, amyotrophic lateral sclerosis (ALS). In 8-wk-old mice that did not yet exhibit motor paralysis, MT-I mRNA expression was already significantly upregulated in the region of the spinal cord responsible for motor paralysis. The expression of another isoform, MT-III, was not changed. In the cerebellum, which is not responsible for motor paralysis in ALS, neither the expression profiles of MT-I nor MT-III were altered. In 16-wk-old mice exhibiting motor paralysis, the expression of MT-I mRNA remained upregulated and the MT-III level tended to be elevated. Although no significant differences were found in the levels of both isoforms in the liver or kidney of 8-wk-old mice, the MT-I mRNA expression level was significantly upregulated in the kidney and liver of 16-wk-old mice. These results indicated that the MT-I isoform, but not the MT-III isoform, is associated with motor neuron death in ALS and suggested that the disease might be a systemic disorder to which the spinal cord is particularly susceptible.
Ono
Shin-Ichi
S
Laboratory of Clinical Pharmacy, College of Pharmacy, Nihon University, Funabashi, Chiba, 274-8555, Japan.
Endo
Yuko
Y
Tokuda
Ei-Ichi
E
Ishige
Kumiko
K
Tabata
Kei-Ichi
K
Asami
Satoru
S
Ito
Yoshihisa
Y
Suzuki
Takashi
T
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics*; D000090023:Metallothionein 3; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D015854:Up-Regulation
D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D008668:Metallothionein