1. Berg JM, Lee C, Chen L, Galvan L, Cepeda C, Chen JY, Penagarikano O, Stein JL, Li A, Oguro-Ando A, Miller JA, Vashisht AA, Starks ME, Kite EP, Tam E, Gdalyahu A, Al-Sharif NB, Burkett ZD, White SA, Fears SC, Levine MS, Wohlschlegel JA, Geschwind DH. {{JAKMIP1, a Novel Regulator of Neuronal Translation, Modulates Synaptic Function and Autistic-like Behaviors in Mouse}}. {Neuron};2015 (Nov 25)
Autism spectrum disorder (ASD) is a heritable, common neurodevelopmental disorder with diverse genetic causes. Several studies have implicated protein synthesis as one among several of its potential convergent mechanisms. We originally identified Janus kinase and microtubule-interacting protein 1 (JAKMIP1) as differentially expressed in patients with distinct syndromic forms of ASD, fragile X syndrome, and 15q duplication syndrome. Here, we provide multiple lines of evidence that JAKMIP1 is a component of polyribosomes and an RNP translational regulatory complex that includes fragile X mental retardation protein, DEAD box helicase 5, and the poly(A) binding protein cytoplasmic 1. JAKMIP1 loss dysregulates neuronal translation during synaptic development, affecting glutamatergic NMDAR signaling, and results in social deficits, stereotyped activity, abnormal postnatal vocalizations, and other autistic-like behaviors in the mouse. These findings define an important and novel role for JAKMIP1 in neural development and further highlight pathways regulating mRNA translation during synaptogenesis in the genesis of neurodevelopmental disorders.
Lien vers le texte intégral (Open Access ou abonnement)
2. Schroeder JC, Reim D, Boeckers TM, Schmeisser MJ. {{Genetic Animal Models for Autism Spectrum Disorder}}. {Curr Top Behav Neurosci};2015 (Nov 25)
Autism spectrum disorder (ASD) affects approximately 1 % of the human population and has a strong genetic component. Hence, the recent discovery of major « ASD genes » has subsequently resulted in the generation of several genetic animal models of ASD. Careful analysis of behavioral phenotypes and characterization of the underlying neurobiological mechanisms in these models should further help us to identify novel therapeutic targets and develop more effective strategies in the future to ameliorate or even reverse core symptoms and comorbidities of ASD. In this review, we will focus on the mutant mouse as animal model and outline how to characterize both behavioral and neurobiological phenotypes in this organism. We will further discuss a selection of major ASD mutant mouse lines. Our conclusions will finally address the current goals and perspectives in the field to obtain a more comprehensive and possibly also converging picture of ASD pathogenesis, which could be most useful for the desired bench-to-bedside strategy of translational medicine for this complex disorder.
