Kcnq2 Knockout mouse models

Encoding Kv7.2, Kcnq2 is the mouse ortholog of human KCNQ2 and supplies the principal subunit of the neuronal M current, a slowly activating, noninactivating potassium conductance that opens near threshold and provides the dominant brake on repetitive firing. Kv7.2 assembles preferentially with Kv7.3, requires PIP2 at a carboxy-terminal site and calmodulin at helices A and B, and is targeted to the axon initial segment and nodes of Ranvier through an ankyrin-G binding motif; muscarinic M1 receptor activation depletes PIP2 and suppresses the current, which is the classical mechanism of cholinergic excitation. Human variants split cleanly into loss-of-function alleles causing benign familial neonatal epilepsy and dominant-negative pore mutations causing developmental and epileptic encephalopathy, so patient knockins are essential where deletion is not. Constitutive nulls die perinatally, mandating floxed alleles with Emx1-Cre or Nex-Cre for adult phenotyping. Kcnq3 and Kcnq5 partially substitute, so measure retigabine-sensitive M current directly.

Whole body loss of Kcnq2 gives the clearest readout when the question is whether the gene is required at all. Follow up tissue work can still move to a conditional allele if lethality or compensation appears.