title: Neuronal death and perinatal lethality in voltage-gated sodium channel alpha(II)-deficient mice.
abstract: 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 NaChalpha(II). NaChalpha(II)(-/-) mice were morphologically and organogenically indistinguishable from their NaChalpha(+/-) littermates. Notwithstanding, NaChalpha(II)(-/-) mice died perinatally with severe hypoxia and massive neuronal apoptosis, notably in the brainstem. Sodium channel currents recorded from cultured neurons of NaChalpha(II)(-/-) mice were sharply attenuated. Death appears to arise from severe hypoxia consequent to the brainstem deficiency of NaChalpha(II). NaChalpha(II) expression is, therefore, redundant for embryonic development but essential for postnatal survival.
authors.affiliation: Department of Biology, University of California San Diego, La Jolla, CA 92093-0366, USA.
authors.forename: R
authors.initials: R
authors.lastname: Planells-Cases
authors.forename: M
authors.initials: M
authors.lastname: Caprini
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: E M
authors.initials: EM
authors.lastname: Rockenstein
authors.forename: R R
authors.initials: RR
authors.lastname: Rivera
authors.forename: C
authors.initials: C
authors.lastname: Murre
authors.forename: E
authors.initials: E
authors.lastname: Masliah
authors.forename: M
authors.initials: M
authors.lastname: Montal
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001933:Brain Stem / Q000473:pathology; D016923:Cell Death; D002478:Cells, Cultured; D005313:Fetal Death; D006624:Hippocampus / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000473:pathology; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D011995:Recombination, Genetic; D015183:Restriction Mapping; D012530:Saxitoxin / Q000493:pharmacokinetics; D015222:Sodium Channels / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D015222:Sodium Channels; D012530:Saxitoxin