Neuronal death and perinatal lethality in voltage-gated sodium channel αII-deficient mice

Neural activity is crucial for cell survival and fine patterning of neuronal connectivity during neurodevelopment, To investigate the role in vivo of sodium channels (NaCh) in these processes, we generated knockout mice deficient in brain NaCh alpha(II). NaCh alpha(II)(-/-) mice were morphologically and organogenically indistinguishable from their NaCh alpha(+/-) littermates. Notwithstanding, NaCh alpha(II)(-/-) mice died perinatally with severe hypoxia and massive neuronal apoptosis, notably in the brainstem. Sodium channel currents recorded from cultured neurons of NaCh alpha(II)(-/-) mice were sharply attenuated. Death appears to arise from severe hypoxia consequent to the brainstem deficiency of NaCh alpha(II). NaCh alpha(II) expression is, therefore, redundant for embryonic development but essential for postnatal survival.