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Sporadic obstructive hydrocephalus in Aqp4 null mice
Author(s) -
Feng Xuechao,
Papadopoulos Marios C.,
Liu Jun,
Li Lihua,
Zhang Di,
Zhang Hongguo,
Verkman A. S.,
Ma Tonghui
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21927
Subject(s) - hydrocephalus , knockout mouse , heterozygote advantage , extravasation , cerebral aqueduct , pathology , medicine , conditional gene knockout , cerebrospinal fluid , evans blue , endocrinology , biology , allele , surgery , genetics , receptor , gene , phenotype
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 ∼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. © 2008 Wiley‐Liss, Inc.