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Un modèle du syndrome de l’X fragile et pour l’autisme (Dr Alain Cohen, Journal International de Médecine)

Seconde cause de déficience intellectuelle (après la trisomie 21), le syndrome de l’X fragile (SXF) est compris actuellement comme un trouble développemental, imputable à une mutation du gène FMR1 (rattaché au chromosome X), gène codant la protéine FMRP qui se trouve « largement impliquée dans le fonctionnement synaptique », rappellent des chercheurs de l’Université française de Bordeaux et de l’Université italienne de Brescia, auteurs d’une étude sur un modèle animal du SXF, publiée dans la revue Autism Research. Le SXF constitue aussi la « cause la plus fréquente d’autisme lié à un facteur monogénique », le gène en question étant précisément ce gène FMR1.

Or grâce aux souris dites KO (knock-out)[1], un modèle animal est désormais disponible (la lignée de souris Fmr1-KO2), et se révèle précieux pour la recherche, à la fois sur le SXF et sur les troubles autistiques. L’équivalent du gène humain FMR1 ayant été inactivé chez cette lignée de souris KO, on compare leur comportement en matière de socialisation et de communication (en particulier par l’analyse informatique de leurs vocalisations, émises dans le domaine des ultra-sons) avec le comportement habituel des souris non KO (dites wild-type, de type sauvage, un terme à rapprocher du mot « neurotypique » employé, par opposition à « autiste », pour l’être humain).

Des anomalies comportementales évoquant l’autisme

En analysant le comportement de ces souris KO, à des âges de moins de 5 semaines, 5 à 10 semaines, et plus de 3 mois (correspondant respectivement dans l’espèce humaine à l’enfance, l’adolescence et l’âge adulte), les auteurs observent « des déficits présents dès « l’adolescence » de la souris » et persistant à l’âge adulte : hyperactivité, altération des émotions, troubles de la mémoire… Correspondant à des troubles de la socialisation chez l’être humain, des altérations des comportements en groupe sont observés seulement chez les souris KO les plus jeunes : durant les deux premières semaines de leur existence, elles émettent des vocalisations (dans la gamme des ultra-sons) « plus longues, comparativement à leurs homologues wild-type, et elles présentent, durant leur  « adolescence », des comportements plus agressifs envers leurs congénères ». Pour les auteurs, ces constats confirment l’intérêt de ces souris KO comme modèle animal du SXF, et les liens entre cette affection génétique et certains « phénotypes sociaux » évoquant avec pertinence l’autisme dès un âge précoce.

[1] http://biotechlerncenter.interpharma.ch/fr/3102-5-des-souris-knock-out-pour-comprendre-les-genes & https://fr.wikipedia.org/wiki/Souris_knock-out

Référence
Gaudissard J et coll.: Behavioral abnormalities in the Fmr1-KO2 mouse model of Fragile X Syndrome: The relevance of early life phases. Autism Research 2017, 10 : 1584–1596.

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