Sporadic obstructive hydrocephalus in Aqp4 null mice

J Neurosci Res. 2009 Apr;87(5):1150-5. doi: 10.1002/jnr.21927.

Abstract

Aquaporin-4 (Aqp4) is a water transport protein expressed in glia and ependymocytes in brain. We report here the unexpected occurrence of severe obstructive hydrocephalus in a random subset of Aqp4 knockout mice. Of 612 Aqp4 knockout mice produced by heterozygote-heterozygote or knockout-knockout breedings, 9.6% of offspring manifested progressive encephalomegaly. Encephalomegaly was never seen in wild-type or Aqp4 heterozygous mice. Examination of the subset encephalomegalic mice revealed marked triventricular hydrocephalus (lateral ventricle size approximately 500 mm(3)), elevated intracranial pressure (19 +/- 3 vs. 6.1 +/- 0.6 mm Hg), and death by age 6 weeks, with a median survival of 28 days. Intraventricular dye injection studies revealed total obstruction of the cerebral aqueduct. Evans blue extravasation studies indicated an intact blood-brain barrier in the hydrocephalic mice. Brain histology revealed reduced ventricular size and ependymocyte disorganization in some nonhydrocephalic Aqp4 null mice. Our studies establish Aqp4 deletion as a predisposing factor for the development of congenital obstructive hydrocephalus in mice. We suggest that AQP4 polymorphisms might also contribute to the development of aqueduct stenosis in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 4 / genetics*
  • Blood-Brain Barrier / pathology
  • Cerebral Aqueduct / pathology
  • Cerebral Ventricles / pathology*
  • Constriction, Pathologic
  • Ependyma / pathology
  • Evans Blue
  • Extravasation of Diagnostic and Therapeutic Materials
  • Genetic Predisposition to Disease
  • Hydrocephalus / genetics*
  • Hydrocephalus / mortality
  • Injections, Intraventricular
  • Intracranial Pressure / genetics
  • Mice
  • Mice, Knockout

Substances

  • Aqp4 protein, mouse
  • Aquaporin 4
  • Evans Blue