Pancreas-specific aquaporin 12 null mice showed increased susceptibility to caerulein-induced acute pancreatitis.
Aquaporin 12 (AQP12) is the most recently identified member of the mammalian AQP family and is specifically expressed in pancreatic acinar cells. In vitro expression studies have revealed that AQP12 is localized at intracellular sites. To determine the physiological roles of AQP12 in the pancreas, we generated knockout mice for this gene (AQP12-KO). No obvious differences were observed under normal conditions between wild-type (WT) and AQP12-KO mice in terms of growth, blood chemistry, pancreatic fluid content, or histology. However, when we induced pancreatitis through the administration of a cholecystokinin-8 (CCK-8) analog, the AQP12-KO mice showed more severe pathological damage to this organ than WT mice. Furthermore, when we analyzed exocytosis in the pancreatic acini using a two-photon excitation imaging method, the results revealed larger exocytotic vesicles (vacuoles) in the acini of AQP12-KO mice at a high CCK-8 dose (100 nM). From these results, we conclude that AQP12 may function in the mechanisms that control the proper secretion of pancreatic fluid following rapid and intense stimulation.
Ohta
Eriko
E
Dept. of Nephrology, Tokyo Medical and Dental Univ., Japan.
Itoh
Tomohiro
T
Nemoto
Tomomi
T
Kumagai
Jiro
J
Ko
Shigeru B H
SB
Ishibashi
Kenichi
K
Ohno
Mayuko
M
Uchida
Keiko
K
Ohta
Akihito
A
Sohara
Eisei
E
Uchida
Shinichi
S
Sasaki
Sei
S
Rai
Tatemitsu
T
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D020346:Aquaporins / Q000172:deficiency*; D002108:Ceruletide; D002766:Cholecystokinin; D004032:Diet; D004198:Disease Susceptibility / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005089:Exocytosis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010179:Pancreas / Q000201:enzymology / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010195:Pancreatitis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D010446:Peptide Fragments; D010539:Permeability; D017785:Photons; D014018:Tissue Distribution; D014867:Water / Q000378:metabolism
C501068:AQP12 protein, mouse; D020346:Aquaporins; D010446:Peptide Fragments; C410885:cholecystokinin 8; D014867:Water; D002108:Ceruletide; D002766:Cholecystokinin; D000681:Amylases