Single amino acid substitution in aquaporin 11 causes renal failure.
Authors Tchekneva EE, Khuchua Z, Davis LS, Kadkina V, Dunn SR, Bachman S, Ishibashi K,
Rinchik EM, Harris RC, Dikov MM, Breyer MD
Submitted By Matthew Breyer on 2/8/2009
Status Published
Journal Journal of the American Society of Nephrology : JASN
Year 2008
Date Published 10/1/2008
Volume : Pages 19(10) : 1955 - 1964
PubMed Reference 18701606
Abstract A screen of recessive mutations generated by the chemical mutagen
n-ethyl-n-nitrosourea (ENU) mapped a new mutant locus (5772SB) termed sudden
juvenile death syndrome (sjds) to chromosome 7 in mice. These mutant mice, which
exhibit severe proximal tubule injury and formation of giant vacuoles in the
renal cortex, die from renal failure, a phenotype that resembles aquaporin 11
(Aqp11) knockout mice. In this report, the ENU-induced single-nucleotide variant
(sjds mutation) is identified. To determine whether this variant, which causes
an amino acid substitution (Cys227Ser) in the predicted E-loop region of
aquaporin 11, is responsible for the sjds lethal renal phenotype, Aqp11-/sjds
compound heterozygous mice were generated from Aqp11 +/sjds and Aqp11 +/-
intercrosses. The compound heterozygous Aqp11 -/sjds offspring exhibited a
lethal renal phenotype (renal failure by 2 wk), similar to the Aqp11 sjds/sjds
and Aqp11-/- phenotypes. These results demonstrate that the identified mutation
causes renal failure in Aqp11 sjds/sjds mutant mice, providing a model for
better understanding of the structure and function of aquaporin 11 in renal

Investigators with authorship
Matthew BreyerJohnson & Johnson
Raymond HarrisVanderbilt University


Aqp11aquaporin 11