PMID- 27684718
OWN - NLM
STAT- Publisher
LR  - 20191120
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 9
DP  - 2016
TI  - Transgenic Mice Expressing MCP-1 by the Urothelium Demonstrate Bladder 
      Hypersensitivity, Pelvic Pain and Voiding Dysfunction: A Multidisciplinary 
      Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study.
PG  - e0163829
LID - 10.1371/journal.pone.0163829 [doi]
LID - e0163829
AB  - Monocyte chemoattractant protein-1 (MCP-1) is one of the key chemokines that play 
      important roles in diverse inflammatory and chronic pain conditions. Interstitial 
      cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating 
      inflammatory condition of the urinary bladder characterized by the hallmark 
      symptoms of pelvic pain and voiding dysfunction. To facilitate IC/BPS research, 
      we used transgenic technology to develop a novel urothelial MCP-1 secretion mouse 
      model (URO-MCP-1). A transgene consisting of the uroplakin II gene promoter and 
      the mouse MCP-1 coding sequence with a secretory element was constructed and 
      microinjected. URO-MCP-1 mice were found to express MCP-1 mRNA in the bladder 
      epithelium and MCP-1 protein in the urine, and developed bladder inflammation 24 
      hours after intravesical administration of a single sub-noxious dose of 
      lipopolysaccharide (LPS). The inflamed bladders of URO-MCP-1 mice exhibited 
      elevated mRNAs for interleukin (IL)-1ss, IL-6, substance P precursor, and nerve 
      growth factor as well as increased macrophage infiltration. In parallel with 
      these phenotypic changes, URO-MCP-1 mice manifested significant functional 
      changes at days 1 and 3 after cystitis induction. These functional changes 
      included pelvic pain as measured by von Frey filament stimulation and voiding 
      dysfunction (increased urinary frequency, reduced average volume voided per 
      micturition, and reduced maximum volume voided per micturition) as measured by 
      micturition cages. Micturition changes remained evident at day 7 after cystitis 
      induction, although these changes were not statistically significant. Control 
      wild-type C57BL/6 mice manifested no clear changes in histological, biochemical 
      and behavioral features after similar cystitis induction with LPS. Taken 
      together, our results indicate that URO-MCP-1 mice are hypersensitive to bladder 
      irritants such as LPS and develop pelvic pain and voiding dysfunction upon 
      cystitis induction, providing a novel model for IC/BPS research.
FAU - Xu, Suming
AU  - Xu S
AD  - Department of Urology, University of Iowa, Iowa City, Iowa, United States of 
      America.
FAU - Wang, Xu
AU  - Wang X
AD  - Department of Urology, University of Iowa, Iowa City, Iowa, United States of 
      America.
FAU - Wang, Yaoqin
AU  - Wang Y
AD  - Department of Urology, University of Iowa, Iowa City, Iowa, United States of 
      America.
FAU - Lutgendorf, Susan
AU  - Lutgendorf S
AD  - Department of Urology, University of Iowa, Iowa City, Iowa, United States of 
      America.
AD  - Department of Psychology, University of Iowa, Iowa City, Iowa, United States of 
      America.
AD  - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa, 
      United States of America.
FAU - Bradley, Catherine
AU  - Bradley C
AD  - Department of Urology, University of Iowa, Iowa City, Iowa, United States of 
      America.
AD  - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa, 
      United States of America.
FAU - Schrepf, Andrew
AU  - Schrepf A
AD  - Department of Psychology, University of Iowa, Iowa City, Iowa, United States of 
      America.
FAU - Kreder, Karl
AU  - Kreder K
AD  - Department of Urology, University of Iowa, Iowa City, Iowa, United States of 
      America.
AD  - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa, 
      United States of America.
FAU - O'Donnell, Michael
AU  - O'Donnell M
AD  - Department of Urology, University of Iowa, Iowa City, Iowa, United States of 
      America.
FAU - Luo, Yi
AU  - Luo Y
AD  - Department of Urology, University of Iowa, Iowa City, Iowa, United States of 
      America.
LA  - eng
GR  - R01 DK100891/DK/NIDDK NIH HHS/United States
GR  - U01 DK082316/DK/NIDDK NIH HHS/United States
GR  - U01 DK082344/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20160929
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
PMC - PMC5042429
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/09/30 06:00
MHDA- 2016/09/30 06:00
PMCR- 2016/09/29
CRDT- 2016/09/30 06:00
PHST- 2016/08/10 00:00 [received]
PHST- 2016/09/14 00:00 [accepted]
PHST- 2016/09/30 06:00 [entrez]
PHST- 2016/09/30 06:00 [pubmed]
PHST- 2016/09/30 06:00 [medline]
PHST- 2016/09/29 00:00 [pmc-release]
AID - PONE-D-16-32006 [pii]
AID - 10.1371/journal.pone.0163829 [doi]
PST - epublish
SO  - PLoS One. 2016 Sep 29;11(9):e0163829. doi: 10.1371/journal.pone.0163829. 
      eCollection 2016.