title: Severe impairment of cerebellum development in mice expressing a dominant-negative mutation inactivating thyroid hormone receptor alpha1 isoform.
abstract: Thyroid hormone deficiency is known to deeply affect cerebellum post-natal development. We present here a detailed analysis of the phenotype of a recently generated mouse model, expressing a dominant-negative TRα1 mutation. Although hormonal level is not affected, the cerebellum of these mice displays profound alterations in neuronal and glial differentiation, which are reminiscent of congenital hypothyroidism, indicating a predominant function of this receptor isoform in normal cerebellum development. Some of the observed effects might result from the cell autonomous action of the mutation, while others are more likely to result from a reduction in neurotrophic factor production.
authors.affiliation: Université de Lyon, CNRS, INRA, Université Claude Bernard Lyon 1, École Normale, Supérieure de Lyon, Institut de Génomique Fonctionnelle de Lyon, France
authors.forename: Teddy
authors.initials: T
authors.lastname: Fauquier
authors.forename: Eva
authors.initials: E
authors.lastname: Romero
authors.forename: Frédéric
authors.initials: F
authors.lastname: Picou
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chatonnet
authors.forename: Xuan-Nhi
authors.initials: XN
authors.lastname: Nguyen
authors.forename: Laure
authors.initials: L
authors.lastname: Quignodon
authors.forename: Frédéric
authors.initials: F
authors.lastname: Flamant
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002531:Cerebellum / Q000254:growth & development*; D003409:Congenital Hypothyroidism / Q000209:etiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009186:Myelin Sheath / Q000502:physiology; D009457:Neuroglia / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology; D051762:PAX2 Transcription Factor / Q000032:analysis; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology; D013569:Synapses / Q000502:physiology; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D020033:Protein Isoforms; D037021:Thyroid Hormone Receptors alpha; D005680:gamma-Aminobutyric Acid