PMID- 10191086
OWN - NLM
STAT- MEDLINE
DCOM- 19990603
LR  - 20071114
IS  - 0888-7543 (Print)
IS  - 0888-7543 (Linking)
VI  - 57
IP  - 1
DP  - 1999 Apr 1
TI  - cDNA and genomic cloning of mouse aquaporin-2: functional analysis of an
      orthologous mutant causing nephrogenic diabetes insipidus.
PG  - 79-83
AB  - As the first step in generating a transgenic mouse model of nephrogenic diabetes 
      insipidus (NDI), we have analyzed the mouse aquaporin-2 (Aqp2) cDNA and gene and 
      generated a mutated Aqp2 orthologous to NDI-causing human AQP2-T126M. Aqp2 cDNA
      was isolated from mouse kidney and encoded a 271-amino-acid protein with 90.4%
      identity to human AQP2. Expression in Xenopus oocytes indicated that Aqp2 encoded
      a mercurial-sensitive, water-selective channel. Northern blot analysis showed a
      single 1.7-kb Aqp2 transcript expressed only in kidney (medulla > cortex);
      transcript expression was increased approximately 20-fold in 48-h water-deprived 
      mice. Immunoblot analysis revealed a 29-kDa glycoprotein in mouse kidney.
      Sequence comparison of the Aqp2 cDNA with a 5.5-kb mouse genomic DNA indicated
      three introns (lengths 2.4, 0.9, and 0.6 kb) separating four exons with
      boundaries at amino acids 120, 175, and 202. Genomic Southern blot analysis
      revealed a single-copy Aqp2 gene. The mutant Aqp2-T126M was water permeable when 
      expressed in Xenopus oocytes, but was retained at the endoplasmic reticulum (ER) 
      in transfected mammalian cells. The chemical chaperone glycerol produced a
      redistribution of Aqp2-T126M from ER to plasma membrane/endosomes. These results 
      establish a basis for an Aqp2-T126M transgenic knock-in model of NDI.
CI  - Copyright 1999 Academic Press.
FAU - Yang, B
AU  - Yang B
AD  - Department of Physiology, Cardiovascular Research Institute, San Francisco,
      California, 94143-0521, USA.
FAU - Ma, T
AU  - Ma T
FAU - Xu, Z
AU  - Xu Z
FAU - Verkman, A S
AU  - Verkman AS
LA  - eng
SI  - GENBANK/AF020519
SI  - GENBANK/AF105336
GR  - DK35124/DK/NIDDK NIH HHS/United States
GR  - HL59198/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genomics
JT  - Genomics
JID - 8800135
RN  - 0 (Aqp2 protein, mouse)
RN  - 0 (Aquaporin 2)
RN  - 0 (Aquaporin 6)
RN  - 0 (Aquaporins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Aquaporin 2
MH  - Aquaporin 6
MH  - Aquaporins/*genetics
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Blotting, Southern
MH  - CHO Cells
MH  - Cloning, Molecular
MH  - Cricetinae
MH  - Diabetes Insipidus, Nephrogenic/*genetics
MH  - Exons
MH  - Gene Expression
MH  - Immunoblotting
MH  - Mice
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Oocytes/cytology/metabolism
MH  - Time Factors
MH  - Tissue Distribution
MH  - Xenopus/metabolism
EDAT- 1999/04/07 00:00
MHDA- 1999/04/07 00:01
CRDT- 1999/04/07 00:00
PHST- 1999/04/07 00:00 [pubmed]
PHST- 1999/04/07 00:01 [medline]
PHST- 1999/04/07 00:00 [entrez]
AID - S0888-7543(99)95759-2 [pii]
AID - 10.1006/geno.1999.5759 [doi]
PST - ppublish
SO  - Genomics. 1999 Apr 1;57(1):79-83. doi: 10.1006/geno.1999.5759.