Auts2-flox Mouse

AUTS2, also known as Autism susceptibility candidate 2, is a crucial gene associated with a wide range of neuropsychological disorders, such as autism spectrum disorders (ASD), intellectual disability (ID), schizophrenia, and epilepsy [2]. It is involved in multiple neurodevelopmental processes. In cell nuclei, it acts as a key transcriptional regulator, while in the cytoplasm, it participates in cerebral corticogenesis, including neuronal migration and neuritogenesis, through controlling cytoskeletal rearrangements. Postnatally, it regulates the number of excitatory synapses to maintain the balance between excitation and inhibition in neural circuits [2]. Genetic models like zebrafish and mice are valuable tools for studying AUTS2 [1,3].

In mouse models, excision of different Auts2 exons led to distinct phenotypes. For example, excision of exon 15 caused breathing abnormalities and neonatal lethality when inactivated throughout the developing brain. Limited inactivation in the cerebral cortex resulted in cortical structure and function abnormalities, including dentate gyrus hypoplasia and abnormal EEG spiking activity [5]. Auts2 -cKO mice, with deletion specifically in Exm1 -positive neurons, exhibited ASD-like behaviors, reduced brain glucose uptake, inhibited pentose phosphate pathway, signs of oxidative stress, and disrupted mitochondrial homeostasis [4]. In zebrafish, auts2a morphants displayed microcephaly, which could be rescued by either the full-length or the C-terminal isoform of AUTS2 [1,3].

In conclusion, AUTS2 plays essential roles in neurodevelopment, regulating processes like neuronal migration, neuritogenesis, and RNA metabolism. Mouse models, especially KO and CKO mouse models, have significantly contributed to understanding its role in diseases such as ASD, intellectual disability, and related neurological disorders. These models help reveal the molecular mechanisms underlying AUTS2 -associated pathologies, providing insights into potential therapeutic strategies for these conditions.