The identification of a novel isoform of EphA4 and ITS expression in SOD1G93Amice.
Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motor neurons, leading to progressive muscle atrophy and fatal paralysis. Mutations in more than 20 genes, including full-length EphA4 (EphA4-FL), have been implicated in this pathogenesis. The present study aimed to identify novel isoforms of EphA4-FL and to investigate the expression of EphA4-FL and its isoforms in the superoxide dismutase 1 (SOD1) mutant mouse model of ALS. Two novel transcripts were verified in mouse and humans. In transfected cells, both transcripts could be translated into proteins, which respectively contained the N- and C-termini of EphA4-FL, referred as EphA4-N and EphA4-C. EphA4-N, which was expressed on the surface of transfected cells, was shown to act as a dominant negative receptor by significantly suppressing the activation of EphA4-FL in vitro. The expression of both EphA4-FL and EphA4-N was significantly higher in the nervous tissue of SOD1G93Acompared to wild-type mice suggesting that both forms are modulated during the disease process.
Queensland Brain Institute, University of Queensland, Qld 4072, Australia.
Jing
J
Zhao
School of Medicine, University of Queensland, Qld 4072, Australia; QIMR Berghofer Medical Research Institute, Qld 4006, Australia.
Andrew W
AW
Boyd
Queensland Brain Institute, University of Queensland, Qld 4072, Australia. Electronic address: p.bartlett@uq.edu.au.
Perry F
PF
Bartlett
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D036122:Receptor, EphA4 / Q000378:metabolism*; D000072105:Superoxide Dismutase-1 / Q000235:genetics
D020033:Protein Isoforms; D012333:RNA, Messenger; C000606291:Sod1 protein, mouse; D000072105:Superoxide Dismutase-1; D036122:Receptor, EphA4
EphA4 receptor; SOD1(G93A) mice; amyotrophic lateral sclerosis; isoforms