@article{918368c2891045dd851aaf6de4248d83,
title = "Loss of MeCP2 causes urological dysfunction and contributes to death by kidney failure in mouse models of rett syndrome",
abstract = "Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction. We then evaluated urological function in a mouse model of RTT and found an abnormal pattern of micturition. Both male and female mice possessing Mecp2 mutations show a decrease in urine output per micturition event. Furthermore, we identified signs of kidney failure secondary to urethral obstruction. Although genetic strain background significantly affects both survival and penetrance of the urethral obstruction phenotype, survival and penetrance of urethral obstruction do not directly correlate. We have identified an additional phenotype caused by loss of MeCP2, urological dysfunction. Furthermore, we urge caution in the interpretation of survival data as an endpoint in preclinical studies, especially where causes of mortality are poorly characterized.",
author = "Ward, {Christopher S.} and Huang, {Teng Wei} and Herrera, {Jos{\'e} A.} and Samaco, {Rodney C.} and Pitcher, {Meagan R.} and Alan Herron and Skinner, {Steven A.} and Kaufmann, {Walter E.} and Glaze, {Daniel G.} and Percy, {Alan K.} and Neul, {Jeffrey L.}",
note = "Funding Information: The authors would like to thank the generous contributions of Yaling Sun, Diana Parra and E. Melissa Arvide for technical help and assistance in generating the animals used for this study. This work was supported by funding from the International Rett Syndrome Foundation (JLN), NIH grants HD062553 (JLN), DP5OD009134 (RCS), HD024064 (BCM IDDRC), HD061222 (AKP), NS066601 (CSW). The Rett Syndrome Natural History Study (U54 HD061222) is a part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS). The Rett Syndrome Natural History Study is funded through collaboration between NCATS, and the Eunice Kennedy Shriver Child Health and Human Development Institute (NICHD). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Development of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2016 Ward et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2016",
month = nov,
day = "1",
doi = "10.1371/journal.pone.0165550",
language = "English (US)",
volume = "11",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",
}