Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome
| Autor: | Walter E. Kaufmann, Jeffrey L. Neul, Meagan R. Pitcher, Rodney C. Samaco, Daniel G. Glaze, Christopher S. Ward, José A. Herrera, Teng-Wei Huang, Alan K. Percy, Steven A. Skinner, Alan Herron |
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| Přispěvatelé: | Landsberger, Nicoletta |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Gerontology Male Kidney Disease Heredity Databases Factual Physiology Genetic Linkage Methyl-CpG-Binding Protein 2 lcsh:Medicine Social Sciences Gene Expression Penetrance Neurodegenerative Urine Congenital Mice 0302 clinical medicine Neurodevelopmental disorder Medicine and Health Sciences 2.1 Biological and endogenous factors Psychology Renal Insufficiency Aetiology lcsh:Science media_common Pediatric Mammals Multidisciplinary Animal Models 3. Good health Body Fluids X-Linked Traits Sex Linkage Vertebrates Female medicine.symptom Anatomy Research Article Urologic Diseases medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Urethral Obstruction General Science & Technology media_common.quotation_subject Urology Bladder Renal and urogenital Urination Rett syndrome Mouse Models Research and Analysis Methods Rodents MECP2 Databases 03 medical and health sciences Rare Diseases Model Organisms Species Specificity medicine Rett Syndrome Genetics Animals Humans Factual Clinical Genetics Animal business.industry Urinary retention lcsh:R Genetic strain Organisms Biology and Life Sciences Kidneys Renal System Urinary Retention medicine.disease Survival Analysis Brain Disorders Disease Models Animal Good Health and Well Being 030104 developmental biology Disease Models Amniotes Developmental Psychology Mutation lcsh:Q Kidney stones business Physiological Processes 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE Ward, CS; Huang, T-W; Herrera, JA; Samaco, RC; Pitcher, MR; Herron, A; et al.(2016). Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome. PLOS ONE, 11(11). doi: 10.1371/journal.pone.0165550. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/4c231034 PLoS ONE, Vol 11, Iss 11, p e0165550 (2016) PloS one, vol 11, iss 11 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0165550. |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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