Distinct early development trajectories in Nf1 ± and Tsc2 ± mouse models of autism

Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction, and repetitive behaviors. Males are three times more likely to be diagnosed with ASD than females, and sex-dependent alterations in behavior and com...

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Main Authors: Helena Ferreira, Sofia Santos, João Martins, Miguel Castelo-Branco, Joana Gonçalves
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Journal of Neurodevelopmental Disorders
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Online Access:https://doi.org/10.1186/s11689-025-09624-6
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Summary:Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction, and repetitive behaviors. Males are three times more likely to be diagnosed with ASD than females, and sex-dependent alterations in behavior and communication have been reported both in clinical and animal research. Animal models are useful for understanding ASD-related manifestations and their associated neurobiological mechanisms. However, even though ASD is diagnosed during childhood, relatively few animal studies have focused on neonatal development. Methods Here, we performed a detailed analysis of neonatal developmental milestones and maternal separation-induced ultrasonic vocalizations (USVs) in two genetic animal models of ASD, neurofibromatosis type 1 (Nf1 ±) and tuberous sclerosis complex 2 (Tsc2 ±). Results Nf1 ± and Tsc2 ± mice display strikingly distinct developmental profiles regarding motor, strength, and coordination skills. Nf1 ± mouse pups mostly show genotype-related differences, whereas Tsc2 ± mouse pups mainly present sexual dimorphisms. Furthermore, we found several differences regarding the number of USVs, frequency modulation, and temporal and spectral profile. Importantly, Nf1 ± animals tend to present sex- and genotype-dependent differences earlier than the Tsc2 ± mouse pups, suggesting distinct developmental curves between these two animal models. Conclusions This study provides a nuanced understanding of how these two ASD models differ in their developmental trajectories. It underscores the importance of studying sex differences and early-life developmental markers, as these could offer crucial insights into ASD's progression and neurobiology. The distinct profiles of these models may help guide more targeted therapeutic strategies in the future.
ISSN:1866-1955