Autres pathologies - page 2 - Publications Scientifiques

Dernière publication 11/03/2020

Recapitulation of the EEF1A2 D252H neurodevelopmental disorder-causing missense

Heterozygous de novo mutations in EEF1A2, encoding the tissue-specific translation elongation factor eEF1A2, have been shown to cause...

Array
(
    [id_prestablog_news] => 1246
    [id_shop] => 1
    [date] => 2020-03-11 00:00:00
    [date_modification] => 2024-02-09 14:15:12
    [langues] => ["1","2"]
    [actif] => 1
    [slide] => 0
    [url_redirect] => 
    [average_rating] => 
    [number_rating] => 
    [author_id] => 1
    [featured] => 0
    [prim_key] => 2450
    [id_lang] => 2
    [title] => Recapitulation of the EEF1A2 D252H neurodevelopmental disorder-causing missense 
    [paragraph] => Recapitulation of the EEF1A2 D252H neurodevelopmental disorder-causing missense mutation in mice reveals a toxic gain of function
    [content] => 
Authors
FCJ Davies, JE Hope, F McLachlan, GF Marshall et al

 Lab
Centre for Genomic & Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
Journal
Human Molecular Genetics
Abstract
Heterozygous de novo mutations in EEF1A2, encoding the tissue-specific translation elongation factor eEF1A2, have been shown to cause neurodevelopmental disorders including often severe epilepsy and intellectual disability. The mutational profile is unusual; ~_50 different missense mutations have been identified but no obvious loss of function mutations, though large heterozygous deletions are known to be compatible with life. A key question is whether the heterozygous missense mutations operate through haploinsufficiency or a gain of function mechanism, an important prerequisite for design of therapeutic strategies. In order both to address this question and to provide a novel model for neurodevelopmental disorders resulting from mutations in EEF1A2, we created a new mouse model of the D252H mutation. This mutation causes the eEF1A2 protein to be expressed at lower levels in brain but higher in muscle in the mice. We compared both heterozygous and homozygous D252H and null mutant mice using behavioural and motor phenotyping alongside molecular modelling and analysis of binding partners. Although the proteomic analysis pointed to a loss of function for the D252H mutant protein, the D252H homozygous mice were more severely affected than null homozygotes on the same genetic background. Mice that are heterozygous for the missense mutation show no behavioural abnormalities but do have sex-specific deficits in body mass and motor function. The phenotyping of our novel mouse lines, together with analysis of molecular modelling and interacting proteins, suggest that the D252H mutation results in a gain of function.
BIOSEB Instruments Used
Aron Test or Four Plates Test (LE830),Grip strength test (BIO-GS3),Rotarod (BX-ROD)
    [meta_description] => 
    [meta_keywords] => https://www.ncbi.nlm.nih.gov/pubmed/?term=Recapitulation+of+the+EEF1A2+D252H+neurodevelopmental+disorder-causing+missense+mutation+in+mice+reveals+a+toxic+gain+of+function
    [meta_title] => 
    [link_rewrite] => recapitulation-of-the-eef1a2-d252h-neurodevelopmental-disorder-causing-missense-mutation-in-mice-reveals-a-toxic-gain-of-function
    [actif_langue] => 1
    [read] => 1114
    [count_comments] => 0
    [id] => 1246
    [categories] => Array
        (
            [96] => Array
                (
                    [id_prestablog_categorie] => 96
                    [title] => Autres pathologies
                    [link_rewrite] => Autres-pathologies
                )

            [2] => Array
                (
                    [id_prestablog_categorie] => 2
                    [title] => Publications
                    [link_rewrite] => publications
                )

            [25] => Array
                (
                    [id_prestablog_categorie] => 25
                    [title] => Thematiques diverses
                    [link_rewrite] => Thematiques-diverses
                )

        )

    [authors] => 
    [paragraph_crop] => Recapitulation of the EEF1A2 D252H neurodevelopmental disorder-causing missense mutation in [...]
    [link_for_unique] => 1
    [products_liaison] => Array
        (
            [588] => Array
                (
                    [name] => Test d'Aron ou 'Four Plates Test'
                    [description_short] => 
Le 'Four Plates Test' ou test d'Aron est une exclusivité Bioseb!
Un outil rapide pour l'évaluation de substances anxiolytiques putatives chez l'animal naïf. Un "must" pour l'étude de l'anxiété, le screening des drogues et le phénotypage.
                    [thumb] => 
                    [img_empty] => /var/www/vhosts/de3310.ispfr.net/bioseb2024/modules/prestablog/views/img/product_link_white.jpg
                    [image_presente] => 1
                    [link] => https://bioseb.com/fr/anxiete-depression/588-aron-test-or-four-plates-test.html
                )

            [48] => Array
                (
                    [name] => Test d'agrippement
                    [description_short] => 
Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
Nouveautés GS4 - 2023: Écran couleur rétroéclairé (meilleure lisibilité), pédale de remise à zéro, durée de batterie optimisée, taille de mémoire augmentée à 500 valeurs, compteur d'animaux, port USB (transfert de données/charge)

                    [thumb] => 
                    [img_empty] => /var/www/vhosts/de3310.ispfr.net/bioseb2024/modules/prestablog/views/img/product_link_white.jpg
                    [image_presente] => 1
                    [link] => https://bioseb.com/fr/activite-systeme-moteur-coordination/48-grip-strength-test.html
                )

            [1326] => Array
                (
                    [name] => Rotarod pour rats et souris
                    [description_short] => 
Le Rotarod offre une méthode facile pour le test de l'activité motrice chez les rongeurs (rats ou souris) - une solution idéale pour étudier les lésions du système nerveux central (SNC), les effets de différentes pathologies et substances pharmacologiques sur l'activité motrice, la résistance à la fatigue, etc. Désormais encore plus simple d'utilisation! La nouvelle interface utilisateur graphique et tactile permet une visualisation claire de la vitesse et des temps associés à chaque piste. Vous pouvez maintenant changer de mode, régler la vitesse et créer des protocoles directement depuis l'écran principal for une une plus grande flexibilité et un maximum de fonctionnalités.

                    [thumb] => 
                    [img_empty] => /var/www/vhosts/de3310.ispfr.net/bioseb2024/modules/prestablog/views/img/product_link_white.jpg
                    [image_presente] => 1
                    [link] => https://bioseb.com/fr/activite-systeme-moteur-coordination/1326-rotarod.html
                )

        )

)
1