title: Impairment of spinal motor neurons in spinocerebellar ataxia type 1-knock-in mice.
abstract: Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of polyglutamine repeats in the Ataxin-1 protein. An accumulating body of cerebellar, histological and behavioral analyses has proven that SCA1-knock-in mice (in which the endogenous Atxn1 gene is replaced with mutant Atxn1 that has abnormally expanded 154 CAG repeats) work as a good tool, which resembles the central nervous system pathology of SCA1 patients. However, the peripheral nervous system pathology of the model mice has not been studied despite the fact that the clinical manifestation is also characterized by peripheral involvement. We show here that spinal motor neurons are degenerated in SCA1-knock-in mice. Histologically, some spinal motor neurons of the SCA1-knock-in mice have polyglutamine aggregates in their nuclei and also thinner and demyelinated axons. Electrophysiological examinations of the mice showed slower nerve conduction velocities in spinal motor neurons and lower amplitudes of muscle action potential, compared to wild-type mice. Consistently, the mice displayed decrease in rearing number and total rearing time. These results suggest that the knock-in mice serve as a definite model that reproduces peripheral involvement and are therefore useful for research on the peripheral nervous system pathology in SCA1 patients.
authors: Department of Orthopedic surgery, University of Gunma Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors: Yasuhiko
authors: Y
authors: Takechi
authors: Tokue
authors: T
authors: Mieda
authors: Akira
authors: A
authors: Iizuka
authors: Syutaro
authors: S
authors: Toya
authors: Nana
authors: N
authors: Suto
authors: Kenji
authors: K
authors: Takagishi
authors: Yoichi
authors: Y
authors: Nakazato
authors: Kazuhiro
authors: K
authors: Nakamura
authors: Hirokazu
authors: H
authors: Hirai
mesh_terms: D000200:Action Potentials; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009431:Neural Conduction; D009687:Nuclear Proteins / Q000235:genetics*; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins