Stéphane Jamain1,2, Konstantin Radyushkin2, Kurt Hammerschmidt3, Sylvie Granon1, Susann Boretius4, Frédérique Varoqueaux2, N. Ramanantsoa5, Muriel Thoby‐Brisson5, Anja Ronnenberg2, Dorina Winter2, Jens Frahm4, Julia Fischer3, Thomas Bourgeron1, Hannelore Ehrenreich2, Nils Brose2
1Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
2Max Planck Institute of Experimental Medicine [Göttingen]
3Deutsches Primatenzentrum, Leibniz-Institut Primatenforschung
4Max-Planck-Institut für Biophysikalische Chemie - Max Planck Institute for Biophysical Chemistry [Göttingen]
5Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement
Tóm tắt
Autism spectrum conditions (ASCs) are heritable conditions characterized by impaired reciprocal social interactions, deficits in language acquisition, and repetitive and restricted behaviors and interests. In addition to more complex genetic susceptibilities, even mutation of a single gene can lead to ASC. Several such monogenic heritable ASC forms are caused by loss-of-function mutations in genes encoding regulators of synapse function in neurons, including
NLGN4
. We report that mice with a loss-of-function mutation in the murine
NLGN4
ortholog
Nlgn4
, which encodes the synaptic cell adhesion protein Neuroligin-4, exhibit highly selective deficits in reciprocal social interactions and communication that are reminiscent of ASCs in humans. Our findings indicate that a protein network that regulates the maturation and function of synapses in the brain is at the core of a major ASC susceptibility pathway, and establish Neuroligin-4-deficient mice as genetic models for the exploration of the complex neurobiological disorders in ASCs.
