Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects.
Mircsof D,Langouët M,Rio M,Moutton S,Siquier-Pernet K,Bole-Feysot C,Cagnard N,Nitschke P,Gaspar L,Žnidarič M,Alibeu O,Fritz A,Wolfer D,Schröter A,Bosshard G,Rudin M,Koester C,Crestani F,Seebeck P,Boddaert N,Prescott K,Hines R,Moss S,Fritschy J,Munnich A,Amiel J,Brown S,Tyagarajan S,Colleaux L
Source :
2015 Nov 16
Pmid / DOI:
26571461
Abstract
The NONO protein has been characterized as an important transcriptional regulator in diverse cellular contexts. Here we show that loss of NONO function is a likely cause of human intellectual disability and that NONO-deficient mice have cognitive and affective deficits. Correspondingly, we find specific defects at inhibitory synapses, where NONO regulates synaptic transcription and gephyrin scaffold structure. Our data identify NONO as a possible neurodevelopmental disease gene and highlight the key role of the DBHS protein family in functional organization of GABAergic synapses.