Scn9a Conditional Knockout mouse models

Nociceptor threshold setting is the province of Scn9a, the mouse ortholog of human SCN9A, encoding Nav1.7, a tetrodotoxin-sensitive alpha subunit expressed in dorsal root and trigeminal ganglion neurons and sympathetic neurons, where slow closed-state inactivation lets it amplify subthreshold depolarizations and act as a threshold channel. Human genetics is unusually decisive: biallelic loss of function produces congenital insensitivity to pain with anosmia, while gain of function missense alleles cause inherited erythromelalgia (hyperpolarized activation) and paroxysmal extreme pain disorder (impaired fast inactivation). Global Scn9a nulls die shortly after birth, so conditional alleles crossed to Advillin-Cre, Nav1.8-Cre, or Wnt1-Cre are standard for adult pain phenotyping, while patient knockins such as I848T model gain of function pharmacology and humanized alleles enable selective blocker and antibody testing. Compensation from Scn10a and Scn11a within the same neurons is real, so match allele class to behavioral or electrophysiological endpoints accordingly.

Conditional deletion of Scn9a limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Scn9a floxed stock yields usable cohorts.