A Transgenic Mouse Model to Selectively Identify α3 Na,K-ATPase Expressing Cells in the Nervous System

Neuroscience. 2019 Feb 1;398:274-294. doi: 10.1016/j.neuroscience.2018.07.018. Epub 2018 Jul 19.

Abstract

The α3 Na+,K+-ATPase (α3NKA) is one of four known α isoforms of the mammalian transporter. A deficiency in α3NKA is linked to severe movement control disorders. Understanding the pathogenesis of these disorders is limited by an incomplete knowledge of α3NKA expression in the brain as well as the challenges associated with identifying living cells that express the isoform for subsequent electrophysiological studies. To address this problem, transgenic mice were generated on the C57BL/6 genetic background, which utilize the mouse α3 subunit gene (Atp1a3) promoter to drive the expression of ZsGreen1 fluorescent protein. Consistent with published results on α3NKA distribution, a ZsGreen1 signal was detected in the brain, but not in the liver, with Atp1a3-ZsGreen1 transgenic mice. The intensity of ZsGreen1 fluorescence in neuronal cell bodies varied considerably in the brain, being highest in the brainstem, deep cerebellar and select thalamic nuclei, and relatively weak in cortical regions. Fluorescence was not detected in astrocytes or white matter areas. ZsGreen1-positive neurons were readily observed in fresh (unfixed) brain sections, which were amenable to patch-clamp recordings. Thus, the α3NKA-ZsGreen1 mouse model provides a powerful tool for studying the distribution and functional properties of α3NKA-expressing neurons in the brain.

Keywords: Atp1a3; ZsGreen1; central nervous system; sodium-potassium ATPase; transgenic mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / enzymology
  • Brain / cytology*
  • Brain / enzymology*
  • Female
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic*
  • Models, Theoretical*
  • Neurons / cytology
  • Neurons / enzymology
  • Patch-Clamp Techniques
  • Promoter Regions, Genetic
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Tissue Culture Techniques
  • White Matter / cytology
  • White Matter / enzymology

Substances

  • Luminescent Proteins
  • Atp1a3 protein, mouse
  • Sodium-Potassium-Exchanging ATPase