Sodium/myo-inositol cotransporter-1 is essential for the development and function of the peripheral nerves

FASEB J. 2005 Nov;19(13):1887-9. doi: 10.1096/fj.05-4192fje. Epub 2005 Sep 20.


Sodium/myo-inositol cotransporter-1 (SMIT-1) is one of the transporters responsible for importing myo-inositol (MI) into the cells. MI is a precursor for a family of signal transduction molecules, phosphatidylinositol, and its derivatives that regulates many cellular functions. SMIT-1 null mice died soon after birth due to respiratory failure, but neonatal lethality was prevented by prenatal maternal MI supplement. Although the lung air sacs were closed, lung development was not significantly affected in the SMIT-1 null mice. The development of the peripheral nerves, including the brachial plexus, facial, vagus, and intercostal nerves, and the phrenic nerve that innervates the diaphragm was severely affected. All of these peripheral nerve abnormalities were corrected by prenatal MI supplement, indicating that MI is essential for the development of peripheral nerve and that neonatal lethality of the SMIT-1 knockout mice is most likely due to abnormal development of the nerves that control breathing. In the adult SMIT-1 deficient mice rescued by MI supplement, MI content in their brain, kidney, skeletal muscle, liver, and sciatic nerve was greatly reduced. The sciatic nerve, in particular, was most dependent on SMIT-1 for the accumulation of MI, and nerve conduction velocity and protein kinase C activity in this tissue were significantly reduced by SMIT-1 deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Female
  • Gene Expression Regulation, Developmental*
  • Genotype
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / physiology*
  • Heterozygote
  • Homozygote
  • Lung / pathology
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Genetic
  • Neurons / metabolism
  • Peripheral Nerves / metabolism
  • Peripheral Nervous System / embryology*
  • Peripheral Nervous System / metabolism
  • Phosphatidylinositols / metabolism
  • Phrenic Nerve / metabolism
  • Polymerase Chain Reaction
  • Protein Kinase C / metabolism
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / pathology
  • Signal Transduction
  • Symporters / genetics*
  • Symporters / metabolism
  • Symporters / physiology*
  • Tissue Distribution


  • Heat-Shock Proteins
  • Membrane Proteins
  • Phosphatidylinositols
  • SLC5A3 protein, mouse
  • Symporters
  • SLC5A3 protein, human
  • Protein Kinase C