Sporadic Obstructive Hydrocephalus in Aqp4 Null Mice

被引:51
作者
Feng, Xuechao [1 ,2 ]
Papadopoulos, Marios C. [3 ]
Liu, Jun [1 ,2 ]
Li, Lihua [1 ,2 ]
Zhang, Di [1 ,2 ]
Zhang, Hongguo [1 ,2 ]
Verkman, A. S. [4 ,5 ]
Ma, Tonghui [1 ,2 ]
机构
[1] NE Normal Univ, Membrane Channel Res Lab, Changchun 130024, Peoples R China
[2] NE Normal Univ, Key Lab Appl Stat MOE, Changchun 130024, Peoples R China
[3] Univ London, Acad Neurosurg Unit, London, England
[4] Univ Calif San Francisco, Dept Med, San Francisco, CA USA
[5] Univ Calif San Francisco, Dept Physiol, San Francisco, CA USA
关键词
aquaporin; aqueduct stenosis; Aqp4; hydrocephalus; ependyma; AQUAPORIN-4 KNOCKOUT MICE; RAT-BRAIN; CONGENITAL HYDROCEPHALUS; EDEMA; DELETION; MODELS;
D O I
10.1002/jnr.21927
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 similar to 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. (C) 2008 Wiley-Liss, Inc.
引用
收藏
页码:1150 / 1155
页数:6
相关论文
共 20 条
[1]   Aquaporin-4 gene deletion in mice increases focal edema associated with staphylococcal brain abscess [J].
Bloch, O ;
Papadopoulos, MC ;
Manley, GT ;
Verkman, AS .
JOURNAL OF NEUROCHEMISTRY, 2005, 95 (01) :254-262
[2]   Accelerated progression of kaolin-induced hydrocephalus in aquaporin-4-deficient mice [J].
Bloch, Orin ;
Auguste, Kurtis I. ;
Manley, Geoffrey T. ;
Verkman, A. S. .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2006, 26 (12) :1527-1537
[3]  
Bruni JE, 1998, MICROSC RES TECHNIQ, V41, P2, DOI 10.1002/(SICI)1097-0029(19980401)41:1<2::AID-JEMT2>3.0.CO
[4]  
2-Z
[5]  
Crews L, 2004, BRAIN PATHOL, V14, P312
[6]   Sex- and region-specific alterations of basal amino acid and monoamine metabolism in the brain of aquaporin-4 knockout mice [J].
Fan, Y ;
Zhang, J ;
Sun, XL ;
Gao, L ;
Zeng, XN ;
Ding, JH ;
Cao, C ;
Niu, L ;
Hu, G .
JOURNAL OF NEUROSCIENCE RESEARCH, 2005, 82 (04) :458-464
[7]   Generation and phenotype of a transgenic knockout mouse lacking the mercurial-insensitive water channel aquaporin-4 [J].
Ma, TH ;
Yang, BX ;
Gillespie, A ;
Carlson, EJ ;
Epstein, CJ ;
Verkman, AS .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (05) :957-962
[8]   Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke [J].
Manley, GT ;
Fujimura, M ;
Ma, TH ;
Noshita, N ;
Filiz, F ;
Bollen, AW ;
Chan, P ;
Verkman, AS .
NATURE MEDICINE, 2000, 6 (02) :159-163
[9]   Aquaporin 4 changes in rat brain with severe hydrocephalus [J].
Mao, Xiaoyan ;
Enno, Terry L. ;
Del Bigio, Marc R. .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2006, 23 (11) :2929-2936
[10]   Regional analysis of the ependyma of the third ventricle of rat by light and electron microscopy [J].
Mathew, T. C. .
ANATOMIA HISTOLOGIA EMBRYOLOGIA, 2008, 37 (01) :9-18