title: Juvenile manifestation of ultrasound communication deficits in the neuroligin-4 null mutant mouse model of autism.
abstract: Neuroligin-4 (Nlgn4) is a member of the neuroligin family of postsynaptic cell adhesion molecules. Loss-of-function mutations of NLGN4 are among the most frequent, known genetic causes of heritable autism. Adult Nlgn4 null mutant (Nlgn4(-/-)) mice are a construct valid model of human autism, with both genders displaying a remarkable autistic phenotype, including deficits in social interaction and communication as well as restricted and repetitive behaviors. In contrast to adults, autism-related abnormalities in neonatal and juvenile Nlgn4(-/-) mice have not been reported yet. The present study has been designed to systematically investigate in male and female Nlgn4(-/-) pups versus wildtype littermates (WT, Nlgn4(+/+)) developmental milestones and stimulus-induced ultrasound vocalization (USV). Neonatal development, followed daily from postnatal days (PND) 4 to 21, including physical development, neurological reflexes and neuromotor coordination, did not yield any differences between Nlgn4(-/-) and their WT littermates. USV in pups (PND8-9) in response to brief separation from their mothers revealed remarkable gender effects, and a genotype influence in females regarding latency to first call. In juveniles (PND22-23), USV monitoring upon exposure to an anesthetized female intruder mouse uncovered a clear genotype effect with reduced USV in Nlgn4(-/-) mice, and again a more prominent phenotype in females. Together, these data support an early manifestation of communication deficits in Nlgn4(-/-) mice that appear more pronounced in immature females with their overall stronger USV as compared to males.
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Anes
authors.initials: A
authors.lastname: Ju
authors.affiliation: Cognitive Ethology Laboratory, German Primate Center, Göttingen, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Hammerschmidt
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Martesa
authors.initials: M
authors.lastname: Tantra
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Dilja
authors.initials: D
authors.lastname: Krueger
authors.affiliation: DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany; Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. Electronic address: ehrenreich@em.mpg.de.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
mesh_terms: D000367:Age Factors; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*; D001522:Behavior, Animal; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency*; D003142:Communication; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D010641:Phenotype; D012737:Sex Factors; D012919:Social Behavior; D013239:Stereotyped Behavior; D014465:Ultrasonics / Q000379:methods; D014828:Vocalization, Animal
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C527118:Nlgn4 protein, mouse
keywords: C57BL/6J; Gender; Neonatal development; Neonatal milestones; Neuroligin-4; Ultrasound or ultrasonic vocalization