Nrxn2 Conditional Knockout mouse models

Although often treated as the minor paralog, Nrxn2 encodes the mouse ortholog of human NRXN2, an alpha and beta neurexin pair whose extracellular LNS and EGF modules bind neuroligins, LRRTMs, and cerebellin adaptors to align presynaptic release machinery with postsynaptic receptor fields. Its cytoplasmic tail terminates in a PDZ-binding motif engaging CASK, linking the adhesion complex to voltage-gated calcium channels and the active zone. Truncating NRXN2 variants have been reported in autism and schizophrenia pedigrees, and alpha-Nrxn2 null mice show altered social behavior and anxiety with region-specific transmission deficits. Design decisions therefore split between conditional alpha-specific exon removal, beta-selective ablation, splice site 4 fixed knockins, and humanization for variant testing. Given strong functional overlap with Nrxn1 and Nrxn3, compound conditional alleles are usually required to unmask phenotypes, and pairing them with an interneuron or projection-specific Cre determines whether readouts are electrophysiological, behavioral, or ultrastructural.

Nrxn2 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.