C1ql2-flox Mouse

C1ql2, a gene encoding a synaptic protein, is a key regulator in synaptic function. It is involved in pathways such as the Bcl11b/C1ql2/Nrxn3(25b+) pathway, which controls mossy fiber-CA3 synapse function, crucial for learning and memory [1]. C1ql2 also serves as an extracellular organizer to recruit functional postsynaptic kainate-type glutamate receptor (KAR) complexes at mossy fiber-CA3 synapses in the hippocampus [2,3,4].

In C1ql2 knockout (KO) or conditional knockout (CKO) mouse models, disruption of C1ql2-Nrxn3(25b+) interaction by expressing a non-binding C1ql2 mutant or deleting Nrxn3 in dentate gyrus granule neurons recapitulates major parts of the Bcl11b as well as C1ql2 mutant phenotype, impairing synaptic vesicle recruitment and long-term potentiation at mossy fiber-CA3 synapses [1]. In C1ql2/3 double-null mice, CA3 synaptic responses lose the slow, KAR-mediated components, and in a temporal lobe epilepsy model, despite mossy fiber sprouting, KARs are not recruited to postsynaptic sites, leading to reduced recurrent circuit activities [2].

In conclusion, C1ql2 plays essential roles in synaptic function, especially in mossy fiber-CA3 synapses, regulating synaptic vesicle recruitment and KAR-mediated synaptic responses. Studies using C1ql2 KO/CKO mouse models have provided insights into its functions in neurodevelopmental and neuropsychiatric disorders associated with synaptic dysfunction, as well as in temporal lobe epilepsy [1,2].