Distinct early development trajectories in Nf1and Tsc2mouse models of autism.

Scientists studied two different mouse models that help us understand autism. They looked at how baby mice developed and the sounds they made when separated from their mothers. The two types of mice (Nf1 and Tsc2) showed very different patterns of development. One type mainly showed differences based on genetics, while the other showed differences between males and females. This research helps us understand that there may be different pathways to autism.

This study examined early developmental patterns in two mouse models of autism spectrum disorder (ASD) - Nf1 and Tsc2. Researchers analyzed neonatal developmental milestones and ultrasonic vocalizations in mouse pups. Results showed distinct developmental profiles between the two models: Nf1 mice primarily displayed genotype-related differences in motor, strength, and coordination skills, while Tsc2 mice mainly showed sex-based differences. Differences in vocalization patterns, including frequency modulation and temporal profiles, were also observed.

Importantly, Nf1 animals showed sex- and genotype-dependent differences earlier in development compared to Tsc2 mice, suggesting different developmental trajectories between these ASD models.

Findings suggest different genetic forms of ASD may have distinct developmental trajectories and sex-dependent presentations. This could inform more targeted early identification strategies and personalized therapeutic approaches based on underlying genetic causes of autism.

Sample size not reported. Study conducted in animal models which may not fully translate to human autism. Limited to two specific genetic models. Unclear methodology details regarding behavioral assessments and measurement protocols.

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.

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). Nf1and Tsc2mice display strikingly distinct developmental profiles regarding motor, strength, and coordination skills. Nf1mouse pups mostly show genotype-related differences, whereas Tsc2mouse pups mainly present sexual dimorphisms. Furthermore, we found several differences regarding the number of USVs, frequency modulation, and temporal and spectral profile.

Importantly, Nf1animals tend to present sex- and genotype-dependent differences earlier than the Tsc2mouse pups, suggesting distinct developmental curves between these two animal models. 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.