Browsing by Author "Winter, D."

In diesem Beitrag begründen wir nach einem Überblick zum Stand der qualitativen Längsschnittforschung zunächst methodologisch das Verfahren einer Mehrebenenrelationierenden Typenbildung. Dieses ermöglicht zweierlei in den Blick zu nehmen: sowohl Veränderungen von zwei Analysedimensionen einer dualen Karriere – den bildungs- und profilbezogenen Orientierungen –, als auch von individuellen Orientierungen der Jugendlichen und von kollektiven Orientierungen ihrer Peers jeweils im zeitlichen Verlauf und in ihren Wechselverhältnissen. In zwei weiteren Kapiteln werden inhaltliche Ergebnisse der Längsschnittauswertungen zunächst zum Wandel und zur Relation der bildungsund profilbezogenen Orientierungen und anschließend zum Stellenwert der Peers für eine duale Karriere dargestellt und an ausgewählten Fällen verdeutlicht. In einem Fazit werden zentrale empirische Befunde knapp zusammengefasst und auf den Stand der Forschung bezogen.

Autism spectrum disorder (ASD) is a frequent neurodevelopmental disorder characterized by variable clinical severity. Core symptoms are qualitatively impaired communication and social behavior, highly restricted interests and repetitive behaviors. Although recent work on genetic mutations in ASD has shed light on the pathophysiology of the disease, classifying it essentially as a synaptopathy, no treatments are available to date. To develop and test novel ASD treatment approaches, validated and informative animal models are required. Of particular interest, in this context are loss-of-function mutations in the postsynaptic cell adhesion protein neuroligin-4 and point mutations in its homologue neuroligin-3 (NL-3) that were found to cause certain forms of monogenic heritable ASD in humans. Here, we show that NL-3-deficient mice display a behavioral phenotype reminiscent of the lead symptoms of ASD: reduced ultrasound vocalization and a lack of social novelty preference. The latter may be related to an olfactory deficiency observed in the NL-3 mutants. Interestingly, such olfactory phenotype is also present in a subgroup of human ASD patients. Tests for learning and memory showed no gross abnormalities in NL-3 mutants. Also, no alterations were found in time spent in social interaction, prepulse inhibition, seizure propensity and sucrose preference. As often seen in adult ASD patients, total brain volume of NL-3 mutant mice was slightly reduced as assessed by magnetic resonance imaging (MRI). Our findings show that the NL-3 knockout mouse represents a useful animal model for understanding pathophysiological events in monogenic heritable ASD and for developing novel treatment strategies in this devastating human disorder.

Autism spectrum conditions (ASCs) are heritable conditions char-acterized by impaired reciprocal social interactions, deficits inlanguage acquisition, and repetitive and restricted behaviors andinterests. In addition to more complex genetic susceptibilities, evenmutation of a single gene can lead to ASC. Several such monogenicheritable ASC forms are caused by loss-of-function mutations ingenes encoding regulators of synapse function in neurons, includ-ingNLGN4. We report that mice with a loss-of-function mutationin the murineNLGN4orthologNlgn4, which encodes the synapticcell adhesion protein Neuroligin-4, exhibit highly selective deficitsin reciprocal social interactions and communication that are rem-iniscent of ASCs in humans. Our findings indicate that a proteinnetwork that regulates the maturation and function of synapses inthe brain is at the core of a major ASC susceptibility pathway, andestablish Neuroligin-4-deficient mice as genetic models for theexploration of the complex neurobiological disorders in ASCs.