title: ALS2/alsin knockout mice and motor neuron diseases.
abstract: Autosomal recessive mutations in the ALS2 gene have been linked to juvenile-onset amyotrophic lateral sclerosis (ALS2), primary lateral sclerosis and juvenile-onset ascending hereditary spastic paraplegia. Except for two recently identified missense mutations, all other mutations in the ALS2 gene lead to a premature stop codon and likely abrogate all the potential functions of alsin, the protein encoded by the ALS2 gene. To study the pathologic mechanisms of ALS2 deficiency, four different lines of ALS2 knockout (ALS2(-/-)) mice have been generated by independent groups. The loss of ALS2/alsin does not have a drastic effect on the survival or function of motor neurons in mice. However, subtle deficits observed in the behavior and pathology of these mice have aided in our understanding of the relationship between alsin and motor neuron dysfunction. In this review, we summarize and reconcile major findings of ALS2(-/-) mice and attempt to place these results within the larger context of modeling recessive movement disorders in mice.
authors: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892-3707, USA. caih@mail.nih.gov
authors: Huaibin
authors: H
authors: Cai
authors: Hoon
authors: H
authors: Shim
authors: Chen
authors: C
authors: Lai
authors: Chengsong
authors: C
authors: Xie
authors: Xian
authors: X
authors: Lin
authors: Wan Jou
authors: WJ
authors: Yang
authors: Jayanth
authors: J
authors: Chandran
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D004705:Endocytosis / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009046:Motor Neurons / Q000502:physiology*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
chemical_list: C512358:Als2 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D020696:rab5 GTP-Binding Proteins