Cbln2-flox Mouse

Cbln2, or Cerebellin-2, is a secreted glycoprotein that functions as an adaptor protein, connecting presynaptic neurexins to postsynaptic ligands such as GluD1. It is involved in regulating synaptic receptor responses, synapse properties, and is crucial for neural circuit functions [1,2]. Cbln2-related signaling pathways play a role in various biological processes, and its study using genetic models like KO or CKO mouse models has been valuable in understanding its functions.

In mice, conditional genetic deletion of Cbln2 in the medial habenula (MHb) impaired synaptic transmission at Cbln2 + synapses in interpeduncular neurons within 3 weeks, and decreased synapse numbers only after 3 months, indicating a functional requirement for Cbln2 in synapses formed by Cbln2-expressing neurons. Cbln2 MHb deletions also decreased spatial learning [5]. Constitutive Cbln2 KO mice display robust compulsive behaviors and decreased brain serotonin levels, and conditional deletion of Cbln2 from dorsal raphe neurons and presynaptic neurons synapsing onto dorsal raphe neurons reproduced these compulsive behaviors [6].

In colorectal cancer, CBLN2 expression is significantly downregulated, and its overexpression can inhibit oncogenic properties of CRC cells in vitro and CRC tumor growth in vivo, and improve the efficiency of immune checkpoint blockade treatment [3]. In hypoxic pulmonary hypertension rats, CBLN2 promotes endothelial-mesenchymal transition by activating the NF-κB/HIF-1α/Twist1 pathway [4].

In conclusion, Cbln2 plays essential roles in neural circuit-related functions, including synaptic transmission, spatial learning, and the regulation of compulsive behaviors. It is also involved in disease-related processes such as colorectal cancer and pulmonary hypertension. Studies using Cbln2 KO/CKO mouse models have been instrumental in revealing these functions, providing insights into the underlying mechanisms of related diseases and potential therapeutic targets.