Distal axonopathy in an alsin-deficient mouse model.
Mutations in Alsin are associated with chronic juvenile amyotrophic lateral sclerosis (ALS2), juvenile primary lateral sclerosis and infantile-onset ascending spastic paralysis. The primary pathology and pathogenic mechanism of the disease remain largely unknown. Here we show that alsin-deficient mice have motor impairment and degenerative pathology in the distal corticospinal tracts without apparent motor neuron pathology. Our data suggest that ALS2 is predominantly a distal axonopathy, rather than a neuronopathy in the central nervous system of the mouse model, implying that alsin plays an important role in maintaining the integrity of the corticospinal axons.
Deng
Han-Xiang
HX
Department of Neurology and Clinical Neurosciences, Northwestern University Institute for Neuroscience, Chicago, IL 60611, USA. h-deng@northwestern.edu
Zhai
Hong
H
Fu
Ronggen
R
Shi
Yong
Y
Gorrie
George H
GH
Yang
Yi
Y
Liu
Erdong
E
Dal Canto
Mauro C
MC
Mugnaini
Enrico
E
Siddique
Teepu
T
D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001369:Axons / Q000473:pathology* / Q000502:physiology; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D005091:Exons; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology; D009154:Mutation; D011247:Pregnancy; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
C512358:Als2 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1