Astn2, encoding astrotactin 2, is a transmembrane neuronal protein highly expressed in the cerebellum. It functions in receptor trafficking, modulates cerebellar Purkinje cell synaptic activity, and is involved in the trafficking and degradation of surface proteins, thus regulating synaptic connectivity and function in neuronal circuits [2,3,4]. Genetic models like knockout (KO) and conditional knockout (cKO) mouse lines are valuable for studying its functions.

Astn2 KO mice show increased exploratory activity, social behavior, and impulsivity, along with decreased despair-and anxiety-like behaviors, which may be related to decreased dopamine contents and increased serotonin or dopamine turnover in specific brain regions. They also exhibit morphological abnormalities such as thinning of neural cell layers in the hippocampus and reduction of neural cell bodies in the prefrontal cortex [1]. Additionally, both global and PC-specific conditional Astn2 KO mice display ASD-like behavioral phenotypes, including decreased separation-induced pup ultrasonic vocalization calls, hyperactivity, repetitive behaviors, and impaired cerebellar-dependent eyeblink conditioning [2,3]. Electrophysiological experiments on Astn2 KO animals suggest alterations in pre-and postsynaptic components of synaptic transmission [2,3].

In conclusion, Astn2 plays a crucial role in regulating emotional and cognitive functions, as well as ASD-like behaviors and cerebellar circuit properties. The Astn2 KO and cKO mouse models have been instrumental in revealing its functions in these aspects, contributing to a better understanding of related neurodevelopmental disorders such as schizophrenia, bipolar disorder, and autism spectrum disorder [1,2,3].

References:

1. Ito, Takahiro, Yoshida, Mikio, Aida, Tomomi, Ozaki, Norio, Noda, Yukihiro. 2023. Astrotactin 2 (ASTN2) regulates emotional and cognitive functions by affecting neuronal morphogenesis and monoaminergic systems. In Journal of neurochemistry, 165, 211-229. doi:10.1111/jnc.15790. https://pubmed.ncbi.nlm.nih.gov/36807153/

2. Hanzel, Michalina, Fernando, Kayla, Maloney, Susan E, Hull, Court, Hatten, Mary E. 2024. Mice lacking Astn2 have ASD-like behaviors and altered cerebellar circuit properties. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2405901121. doi:10.1073/pnas.2405901121. https://pubmed.ncbi.nlm.nih.gov/39150780/

3. Hanzel, Michalina, Fernando, Kayla, Maloney, Susan E, Hull, Court, Hatten, Mary E. 2024. Mice lacking Astn2 have ASD-like behaviors and altered cerebellar circuit properties. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.02.18.580354. https://pubmed.ncbi.nlm.nih.gov/38405978/

4. Behesti, Hourinaz, Fore, Taylor R, Wu, Peter, Hull, Court, Hatten, Mary E. 2018. ASTN2 modulates synaptic strength by trafficking and degradation of surface proteins. In Proceedings of the National Academy of Sciences of the United States of America, 115, E9717-E9726. doi:10.1073/pnas.1809382115. https://pubmed.ncbi.nlm.nih.gov/30242134/