title: Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.
abstract: BACKGROUND
  Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4) but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone) in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2). To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO) did not find gross neurological alterations, possibly due to compensatory mechanisms.
  
  
  OBJECTIVE
  This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed.
  
  
  RESULTS
  Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice). No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction) and skeletal muscle (33% reduction), but not in the cerebellum where other deiodinase (type 1) is expressed.
  
  
  CONCLUSIONS
  The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders.
authors.affiliation: Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: Bárez-López
authors.affiliation: Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bosch-García
authors.affiliation: Trastornos del Desarrollo y Maduración Neurológica, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain; Departamento de Anatomía, Histología y Neurociencia, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Gómez-Andrés
authors.affiliation: Trastornos del Desarrollo y Maduración Neurológica, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain; Departamento de Anatomía, Histología y Neurociencia, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Pulido-Valdeolivas
authors.affiliation: Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Montero-Pedrazuela
authors.affiliation: Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Obregon
authors.affiliation: Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Guadaño-Ferraz
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D005684:Gait / Q000235:genetics / Q000502:physiology; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D008124:Locomotion / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D014284:Triiodothyronine; D007453:Iodide Peroxidase; D013974:Thyroxine
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