Ajap1-KO Mouse

Ajap1, also known as SHREW1, is an integral membrane protein associated with adherens junctions. It is involved in multiple biological processes and pathways. In neurons, it binds to γ -aminobutyric acid type B receptors (GBRs), regulating neurotransmitter release at synapses [1]. It also appears to play a role in tumor-related processes, potentially acting as a tumor suppressor in various malignancies, such as hepatocellular carcinoma, breast cancer, and gliomas [3,4,5].

In a study of Ajap1 -/- and Ajap1W183C/+ mice, the lack of Ajap1 or the presence of the p.(W183C) variant led to decreased presynaptic GBR levels. This resulted in reduced GBR-mediated presynaptic inhibition at excitatory and inhibitory synapses, as well as impaired synaptic plasticity, highlighting its role in trans-synaptic control of neurotransmitter release [1]. In epileptic mouse models, down-regulation of Ajap1 was observed in the neocortex and hippocampus. Overexpression of Ajap1 reduced the frequency of spontaneous seizures, while its inhibition increased the incidence rate, suggesting its involvement in epilepsy pathogenesis [2].

In summary, Ajap1 is crucial for trans-synaptic regulation of neurotransmitter release and may be involved in the development of epilepsy. The use of gene knockout (KO) mouse models has been instrumental in revealing these functions, providing insights into its role in these specific disease-related biological processes.