title: Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors.
abstract: Thyroid hormone (TH) plays a key role in the developing brain, including the cerebellum. TH deficiency induces organizational changes of the cerebellum, causing cerebellar ataxia. However, the mechanisms causing these abnormalities are poorly understood. Various animal models have been used to study the mechanism. Lacking dual oxidase (DUOX) and its maturation factor (DUOXA) are major inducers of congenital hypothyroidism. Thus, this study examined the organizational changes of the cerebellum using knockout mice of the Duoxa gene (Duoxa-/-).
  
  
  
  The morphological, behavioral, and electrophysiological changes were analyzed in wild type (Wt) and Duoxa-deficient (Duoxa-/-) mice from postnatal day (P) 10 to P30. To detect the changes in the expression levels of presynaptic proteins, Western blot analysis was performed.
  
  
  
  The proliferation and migration of granule cells was delayed after P15 in Duoxa-/- mice. However, these changes disappeared by P25. Although the cerebellar structure of Duoxa-/- mice was not significantly different from that of Wt mice at P25, motor coordination was impaired. It was also found that the amplitude of paired-pulse facilitation at parallel fiber-Purkinje cell synapses decreased in Duoxa-/- mice, particularly at P15. There were no differences between expression levels of presynaptic proteins regulating neurotransmitter release at P25.
  
  
  
  These results indicate that the anatomical catch-up growth of the cerebellum did not normalize its function because of the disturbance of neuronal circuits by the combined effect of hypothyroidism and functional disruption of the DUOX/DUOXA complex.
authors.affiliation: 1 Department of Integrative Physiology, Gunma University Graduate School of Medicine , Maebashi, Japan .
authors.forename: Izuki
authors.initials: I
authors.lastname: Amano
authors.affiliation: 1 Department of Integrative Physiology, Gunma University Graduate School of Medicine , Maebashi, Japan .
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takatsuru
authors.affiliation: 1 Department of Integrative Physiology, Gunma University Graduate School of Medicine , Maebashi, Japan .
authors.forename: Syutaro
authors.initials: S
authors.lastname: Toya
authors.affiliation: 1 Department of Integrative Physiology, Gunma University Graduate School of Medicine , Maebashi, Japan .
authors.forename: Asahi
authors.initials: A
authors.lastname: Haijima
authors.affiliation: 1 Department of Integrative Physiology, Gunma University Graduate School of Medicine , Maebashi, Japan .
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Iwasaki
authors.affiliation: 2 Department of Medicine, The University of Chicago , Chicago, Illinois.|3 Division of Gastroenterology, Department of Internal Medicine, University of Michigan , Ann Arbor, Michigan.
authors.forename: Helmut
authors.initials: H
authors.lastname: Grasberger
authors.affiliation: 2 Department of Medicine, The University of Chicago , Chicago, Illinois.|4 Department of Pediatrics, The University of Chicago , Chicago, Illinois.|5 Department of Genetics, The University of Chicago , Chicago, Illinois.
authors.forename: Samuel
authors.initials: S
authors.lastname: Refetoff
authors.affiliation: 1 Department of Integrative Physiology, Gunma University Graduate School of Medicine , Maebashi, Japan .
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Koibuchi
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: C560186:DUOXA1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins