Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism.
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.
Jamain
Stephane
S
Abteilung Molekulare Neurobiologie and Division für Klinische Neurowissenschaften, Max-Planck-Institut für Experimentelle Medizin, 37075 Göttingen, Germany.
Radyushkin
Konstantin
K
Hammerschmidt
Kurt
K
Granon
Sylvie
S
Boretius
Susann
S
Varoqueaux
Frederique
F
Ramanantsoa
Nelina
N
Gallego
Jorge
J
Ronnenberg
Anja
A
Winter
Dorina
D
Frahm
Jens
J
Fischer
Julia
J
Bourgeron
Thomas
T
Ehrenreich
Hannelore
H
Brose
Nils
N
D000595:Amino Acid Sequence; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology*; D001921:Brain / Q000033:anatomy & histology; D002352:Carrier Proteins / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal; D003142:Communication; D004195:Disease Models, Animal; D008565:Membrane Proteins / Q000235:genetics*; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009929:Organ Size; D012919:Social Behavior; D013569:Synapses / Q000502:physiology; D014465:Ultrasonics; D014828:Vocalization, Animal
D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; C527118:Nlgn4 protein, mouse