Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome

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 i...

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Bibliographic Details
Published in:PloS one 2016-11, Vol.11 (11), p.e0165550-e0165550
Main Authors: Ward, Christopher S, Huang, Teng-Wei, Herrera, José A, Samaco, Rodney C, Pitcher, Meagan R, Herron, Alan, Skinner, Steven A, Kaufmann, Walter E, Glaze, Daniel G, Percy, Alan K, Neul, Jeffrey L
Format: Article
Language:English
Subjects:
Animal models
Animal sciences
Animals
Autonomic nervous system
Biology and Life Sciences
Bladder
Catheterization
Cerebral palsy
Child & adolescent psychiatry
Databases, Factual
Developmental biology
Disease Models, Animal
Female
Gene Expression
Health aspects
Hospitals
Humans
Kidney failure
Kidney stones
Laboratory animals
Lethality
Male
MeCP2 protein
Medical research
Medical schools
Medicine
Medicine and Health Sciences
Methyl-CpG binding protein
Methyl-CpG-Binding Protein 2 - deficiency
Methyl-CpG-Binding Protein 2 - genetics
Mice
Mouse devices
Mutation
Nephrolithiasis
Nervous system
Neurodevelopmental disorders
Pediatrics
Penetrance
Physicians
Quantitative genetics
Renal failure
Renal Insufficiency - complications
Renal Insufficiency - genetics
Renal Insufficiency - mortality
Renal Insufficiency - physiopathology
Research and Analysis Methods
Rett syndrome
Rett Syndrome - complications
Rett Syndrome - genetics
Rett Syndrome - mortality
Rett Syndrome - physiopathology
Social Sciences
Species Specificity
Studies
Survival
Survival Analysis
Urethral Obstruction - complications
Urethral Obstruction - genetics
Urethral Obstruction - mortality
Urethral Obstruction - physiopathology
Urinary bladder
Urinary Retention - complications
Urinary Retention - genetics
Urinary Retention - mortality
Urinary Retention - physiopathology
Urinary tract
Urinary tract infections
Urination
Urine
Urogenital system
Zoology
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Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0165550