PMID- 19538300
OWN - NLM
STAT- MEDLINE
DCOM- 20090803
LR  - 20131121
IS  - 1749-6632 (Electronic)
IS  - 0077-8923 (Linking)
VI  - 1165
DP  - 2009 May
TI  - Insights into driving forces and paracellular permeability from claudin-16 
      knockdown mouse.
PG  - 148-51
LID - 10.1111/j.1749-6632.2009.04041.x [doi]
AB  - Tight junction (TJ) properties are determined by membrane protein complexes of 
      neighboring cells that form both a barrier and a selective pathway for 
      paracellular substrate transport. Our previous work supports the view that 
      paracellular permeability changes in the thick ascending limb (TAL) may underlie 
      the mechanism for familial hypomagnesemia with hypercalciuria and 
      nephrocalcinosis (FHHNC), a rare autosomal recessive disease linked to mutations 
      in claudin-16 (CLDN16) and claudin-19 (CLDN19). CLDN16 knockdown (KD) mice are 
      lacking CLDN16 expression by transgenic RNA interference. We observed that the 
      transport defect for Mg(2+) and Ca(2+) in this animal model is caused by a loss 
      of paracellular cation selectivity. The permeability ratio for Na(+) over Cl(-) 
      in KD mice was lower by a factor of two without a change in paracellular 
      conductance, compared to wild type (WT). This resulted in a collapse of the 
      transepithelial voltage, which is the driving force for Mg(2+) and Ca(2+) 
      absorption in TAL. Since CLDN16 KD mice revealed lower blood pressure and an 
      increased aldosterone plasma concentration, we hypothesize that the reduction in 
      paracellular selectivity could allow backflow of Na(+) and Cl(-) into the lumen 
      of the TAL, thus enhancing the distal NaCl load and challenging the organism with 
      a latent NaCl loss.
FAU - Shan, Qixian
AU  - Shan Q
AD  - Physiologisches Institut der Christian-Albrechts-Universitat, Kiel, Germany.
FAU - Himmerkus, Nina
AU  - Himmerkus N
FAU - Hou, Jianghui
AU  - Hou J
FAU - Goodenough, Daniel A
AU  - Goodenough DA
FAU - Bleich, Markus
AU  - Bleich M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Claudins)
RN  - 0 (Membrane Proteins)
RN  - 0 (claudin 16)
RN  - 9NEZ333N27 (Sodium)
RN  - I38ZP9992A (Magnesium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Cell Membrane Permeability/*genetics
MH  - Claudins
MH  - Magnesium/metabolism
MH  - Membrane Proteins/*genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - RNA Interference
MH  - Sodium/metabolism
MH  - Tight Junctions/metabolism
EDAT- 2009/06/23 09:00
MHDA- 2009/08/04 09:00
CRDT- 2009/06/23 09:00
PHST- 2009/06/23 09:00 [entrez]
PHST- 2009/06/23 09:00 [pubmed]
PHST- 2009/08/04 09:00 [medline]
AID - NYAS04041 [pii]
AID - 10.1111/j.1749-6632.2009.04041.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2009 May;1165:148-51. doi: 10.1111/j.1749-6632.2009.04041.x.