PMID- 29407172
OWN - NLM
STAT- MEDLINE
DCOM- 20180323
LR  - 20201201
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 497
IP  - 1
DP  - 2018 Feb 26
TI  - Nephron segment-specific gene expression using AAV vectors.
PG  - 19-24
LID - S0006-291X(18)30192-X [pii]
LID - 10.1016/j.bbrc.2018.01.169 [doi]
AB  - AAV9 vector provides efficient gene transfer in all segments of the renal 
      nephron, with minimum expression in non-renal cells, when administered 
      retrogradely via the ureter. It is important to restrict the transgene expression 
      to the desired cell type within the kidney, so that the physiological endpoints 
      represent the function of the transgene expressed in that specific cell type 
      within kidney. We hypothesized that segment-specific gene expression within the 
      kidney can be accomplished using the highly efficient AAV9 vectors carrying the 
      promoters of genes that are expressed exclusively in the desired segment of the 
      nephron in combination with administration by retrograde infusion into the kidney 
      via the ureter. We constructed AAV vectors carrying eGFP under the control of: 
      kidney-specific cadherin (KSPC) gene promoter for expression in the entire 
      nephron; Na(+)/glucose co-transporter (SGLT2) gene promoter for expression in the 
      S1 and S2 segments of the proximal tubule; sodium, potassium, 2 chloride 
      co-transporter (NKCC2) gene promoter for expression in the thick ascending limb 
      of Henle's loop (TALH); E-cadherin (ECAD) gene promoter for expression in the 
      collecting duct (CD); and cytomegalovirus (CMV) early promoter that provides 
      expression in most of the mammalian cells, as control. We tested the specificity 
      of the promoter constructs in vitro for cell type-specific expression in mouse 
      kidney cells in primary culture, followed by retrograde infusion of the AAV 
      vectors via the ureter in the mouse. Our data show that AAV9 vector, in 
      combination with the segment-specific promoters administered by retrograde 
      infusion via the ureter, provides renal nephron segment-specific gene expression.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Asico, Laureano D
AU  - Asico LD
AD  - Department of Medicine, The George Washington University, Washington, DC, USA.
FAU - Cuevas, Santiago
AU  - Cuevas S
AD  - Department of Medicine, The George Washington University, Washington, DC, USA.
FAU - Ma, Xiaobo
AU  - Ma X
AD  - Department of Medicine, The George Washington University, Washington, DC, USA.
FAU - Jose, Pedro A
AU  - Jose PA
AD  - Department of Medicine, The George Washington University, Washington, DC, USA; 
      Department of Pharmacology and Physiology, The George Washington University, 
      Washington, DC, USA.
FAU - Armando, Ines
AU  - Armando I
AD  - Department of Medicine, The George Washington University, Washington, DC, USA.
FAU - Konkalmatt, Prasad R
AU  - Konkalmatt PR
AD  - Department of Medicine, The George Washington University, Washington, DC, USA. 
      Electronic address: prk@gwu.edu.
LA  - eng
GR  - R01 DK039308/DK/NIDDK NIH HHS/United States
GR  - P01 HL068686/HL/NHLBI NIH HHS/United States
GR  - R01 HL023081/HL/NHLBI NIH HHS/United States
GR  - R01 DK090918/DK/NIDDK NIH HHS/United States
GR  - R37 HL023081/HL/NHLBI NIH HHS/United States
GR  - R01 HL092196/HL/NHLBI NIH HHS/United States
GR  - P01 HL074940/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180131
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Dependovirus/*growth & development
MH  - Gene Expression Regulation/*genetics
MH  - *Gene Transfer Techniques
MH  - Genes, Viral/*genetics
MH  - Genetic Therapy/methods
MH  - Genetic Vectors
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nephrons/*metabolism/*virology
PMC - PMC5893140
MID - NIHMS949538
OTO - NOTNLM
OT  - AAV
OT  - Promoters
OT  - Renal gene transfer
COIS- Conflicts of interest The authors have declared that no conflict of interest 
      exists.
EDAT- 2018/02/07 06:00
MHDA- 2018/03/24 06:00
PMCR- 2018/04/10
CRDT- 2018/02/07 06:00
PHST- 2018/01/11 00:00 [received]
PHST- 2018/01/27 00:00 [accepted]
PHST- 2018/02/07 06:00 [pubmed]
PHST- 2018/03/24 06:00 [medline]
PHST- 2018/02/07 06:00 [entrez]
PHST- 2018/04/10 00:00 [pmc-release]
AID - S0006-291X(18)30192-X [pii]
AID - 10.1016/j.bbrc.2018.01.169 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Feb 26;497(1):19-24. doi: 
      10.1016/j.bbrc.2018.01.169. Epub 2018 Jan 31.