NDI Flashcards
NDI gene
12q13.12
NDI gene codes for AQP2 a..
271 amino acid protein (Asai et al., 2012)
Prevalence of NDI
1 in 1,000,000
Percent of NDI caused by mutation in AQP2 gene (Knoers, 2012)
10%
AQP2 facilitates the transport of water in..
the principal cells of the collecting duct in the kidney
AQP2 is important in
Concentrating urine in response to ADH
AQP2 protein has 6 TMD with..
both terminal ends of the protein inside the cell
Similar to other members of major intrinsic protein family
AQP2 first and third intracellular loops contain..
NPA motif
NPA motif
facilitates transfer of water in single file by Grotthus mechanism through the channel
NDI arises when..
Failure to recruit functional AQP2 to the apical membrane of the principal cells
NDI symptoms
Polyuria, polydipsia, increase serum osmolality and decrease urine osmolality
Reduced absorption of the kidneys resulting from AQP2 mutations leads to..
severe risk of dehydration
Treatment for NDI
Pharmacological and dietary restriction methods
Mutations that cause NDI are mainly
Missense and occur mostly between the first and last TMD, segment that forms AQP2 water pore results in loss of function of the protein
Example mutation (Duzenli et al 2012)
L137P located in the TMD causes misfolding of the protein in the tertiary structure leaving hydrophobic regions on the surface of the cell - useless as a water channel
Mulders et al 1997 mutation
A147T less stable than WT, exhibited some functionality when tested in Xenopus oocytes
Concluded misrouting of the channel when being upregulated so it doesn’t reach apical membrane in response to ADH
