Ank3-flox Mouse

ANK3, which encodes multiple isoforms of ankyrin-G, is crucial for neuronal development and signaling [1,2]. Alternative splicing of ANK3 gives rise to different ankyrin-G isoforms with distinct expression patterns, and it is involved in various biological processes related to the nervous system [2].

In gene-related disease studies, ANK3 variants are associated with multiple neurodevelopmental phenotypes. Heterozygous missense variants are linked to autism spectrum disorder, while more severe phenotypes are caused by isoform-dependent loss-of-function variants [1]. Mono-or biallelic ANK3 variants result in non-specific syndromic intellectual disability, with biallelic variants leading to a more severe phenotype, including language delay, autism spectrum disorder, intellectual disability, and other symptoms [2]. In an Ank3 mouse model (Ank3-1b KO), deletion of a BD-associated variant leads to absence epilepsy and changes in neocortical oscillation, with abnormal sleep, hyperactivity, and repetitive behaviors accompanied by increased slow gamma power [3]. A mouse model with a missense p.W1989R mutation in Ank3 shows reduced inhibitory signaling and increased pyramidal cell excitability, mimicking BD symptoms in humans, and lithium treatment can normalize neuronal excitability [4].

In conclusion, ANK3 plays a vital role in neuronal development and signaling. Studies using gene-knockout mouse models have significantly enhanced our understanding of its role in neurodevelopmental disorders, bipolar disorder, and epilepsy, providing insights into potential therapeutic targets and pathogenic mechanisms related to these diseases.