Tanc2-flox Mouse

Tanc2, encoding a large multi-domain postsynaptic scaffold protein, is crucial for dendrite formation in synaptic plasticity [2]. It interacts with multiple postsynaptic density (PSD) proteins, playing a significant role in regulating dendritic spines and excitatory synapse formation [5]. Tanc2 is also involved in the mTOR signaling pathway, directly inhibiting mTOR, which is critical for neural development [3].

In zebrafish, tanc2 knockout leads to increased larval brain size and body length, an excitatory/inhibitory (E/I) imbalance with increased glutamatergic neurons, sleep disturbances in larvae, and autism-like behaviors in adults such as anxiolytic-behavior, reduced aggression, and impaired social preference [1]. In mice, Tanc2-null embryos are lethal, while Tanc2-haploinsufficient mice display mTORC1/2 hyperactivity, synaptic and behavioral deficits that can be reversed by mTOR-inhibiting rapamycin [3]. In Drosophila, knockdown of TANC2 increases susceptibility to seizure-like behavior [4].

In summary, Tanc2 is essential for normal neurodevelopment through its role in synaptic plasticity and regulation of the mTOR signaling pathway. Animal models, especially gene-knockout models in zebrafish and mice, have revealed its significant contributions to neural development and provided insights into neurodevelopmental and psychiatric disorders associated with Tanc2 mutations, such as autism, intellectual disability, epilepsy, and related behavioral problems [1-5, 8].