title: Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice.
abstract: Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Villares
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Gutiérrez
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Agnes
authors.initials: A
authors.lastname: Fütterer
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Varvara
authors.initials: V
authors.lastname: Trachana
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gutiérrez del Burgo
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain cmartineza@cnb.csic.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez-A
mesh_terms: D000107:Acetylation; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001921:Brain / Q000002:abnormalities*; D001927:Brain Diseases / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D002972:Cleft Palate / Q000196:embryology / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C120687:Dido protein, mouse; D020033:Protein Isoforms; D014157:Transcription Factors; D014404:Tubulin
keywords: brain patterning; ciliopathies; perinatal lethality
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