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: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
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| Series: | Journal of Neurodevelopmental Disorders |
| Subjects: | |
| 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. |
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| ISSN: | 1866-1955 |