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AQP4, the main subset of the aquaporin water channel family in the brain

RIKEN BRC September 2017
Mouse of the Month

 

AQP4, the main subset of the aquaporin water channel family in the brain

C57BL/6N-Aqp4<tm1Tsna> (RBRC10054, flox)
C57BL/6N-Aqp4<tm1.1Tsna> (RBRC10053, KO)

201709

Courtesy of Mika Terumitsu-Tsujita, Ph.D.

Confocal laser scanning microscopy showing a cellular and subcellular distribution of AQP4 in microslicer sections. Specificity and overall distribution of AQP4 was determined by triple immunofluorescence with AQP4 (magenta), astrocyte marker 3PGDH (blue) and with neuron marker Map2 (green) in the hippocampal CA1 (CA1) and Cerebellum (Cb) regions. Characteristic labeling was observed in the wild-type(WT) mouse brain but not in the AQP4-KO mouse brain. AQP4 is in a cell surface of astrocytes, particularly abundant in perivascular and peri-Purkinje cell processes.

 

The aquaporin(AQP) family is a large collection of integral membrane proteins that enable the movement of water and other small, neutral solutes across biological membranes. Mammalian AQPs consist of 13 homologous members with varying degrees of similarity [1]. AQP4 is the main subset in the brain, particularly in glial astrocytes where it is highly expressed in the perivascular and subpial endfeet [2]. Terumitsu-Tsujita and her colleagues generated AQP4 knockout mice and observed a significant suppression of neural activity-dependent extracellular space volume change which is associated with astrocyte swelling [3]. They also found that water influx into the cerebrospinal fluid is regulated by AQP4 and not by AQP1, strongly supporting the idea that AQP4 regulates water homeostasis in the peri-capillary space [4]. Furthermore, they developed a PET ligand for AQP4 imaging based on TGN-020, a potent AQP4 inhibitor. Utilizing [11C]-TGN-020, PET images were successfully generated in wild type and AQP4 null mice [5].

 

Depositor : Mika Terumitsu-Tsujita, Ph.D.
Department of Functional Neurology and Neurosurgery
Center for Integrated Human Brain Science, University of Niigata
Strain name : C57BL/6N-Aqp4<tm1Tsna> (flox mice)
RBRC No. : RBRC10054
Strain name : C57BL/6N-Aqp4<tm1.1Tsna> (KO mice)
RBRC No. : RBRC10053
References : [1] Huber VJ, Tsujita M, Nakada T. Aquaporins in drug discovery and pharmacotherapy. Mol Aspects Med.; 33(5-6):691-703, 2012.
[2] Nakada T. Virchow-Robin space and aquaporin-4: new insights on an old friend. Croat Med J.; 55(4):328-36, 2014.
[3] Kitaura H, Tsujita M, Huber VJ, Kakita A, Shibuki K, Sakimura K, Kwee IL, Nakada T. Activity-dependent glial swelling is impaired in aquaporin-4 knockout mice. Neurosci Res.; 64(2):208-12, 2009.
[4] Igarashi H, Tsujita M, Kwee IL, Nakada T. Water influx into cerebrospinal fluid is primarily controlled by aquaporin-4, not by aquaporin-1: 17O JJVCPE MRI study in knockout mice. Neuroreport; 25(1):39-43, 2014.
[5] Nakamura Y, Suzuki Y, Tsujita M, Huber VJ, Yamada K, Nakada T. Development of a Novel Ligand, [C]TGN-020, for Aquaporin 4 Positron Emission Tomography Imaging. ACS Chem Neurosci.; 2(10):568-571, 2011.

 

September 2017
Contact: Shinya Ayabe, Ph.D.
Experimental Animal Division, RIKEN BioResource Center
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