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Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats
- Source :
- Journal of Neurodevelopmental Disorders
- Publisher :
- Springer Nature
-
Abstract
- Background Rett Syndrome (RTT) is a neurodevelopmental disease caused by the disruption of the MECP2 gene. Several mouse models of RTT have been developed with Mecp2 disruptions. Although the mouse models are widely used in RTT research, results obtained need to be validated in other species. Therefore, we performed these studies to characterize phenotypes of a novel Mecp2−/Y rat model and compared them with the Mecp2tm1.1Bird mouse model of RTT. Methods RTT-like phenotypes were systematically studied and compared between Mecp2−/Y rats and Mecp2−/Y mice. In-cage conditions of the rats were monitored. Grip strength and spontaneous locomotion were used to evaluate the motor function. Three-chamber test was performed to show autism-type behaviors. Breathing activity was recorded with the plethysmograph. Individual neurons in the locus coeruleus (LC) were studied in the whole-cell current clamp. The lifespan of the rats was determined with their survival time. Results Mecp2−/Y rats displayed growth retardation, malocclusion, and lack of movements, while hindlimb clasping was not seen. They had weaker forelimb grip strength and a lower rate of locomotion than the WT littermates. Defects in social interaction with other rats were obvious. Breathing frequency variation and apnea in the null rats were significantly higher than in the WT. LC neurons in the null rats showed excessive firing activity. A half of the null rats died in 2 months. Most of the RTT-like symptoms were comparable to those seen in Mecp2−/Y mice, while some appeared more or less severe. The findings that most RTT-like symptoms exist in the rat model with moderate variations and differences from the mouse models support the usefulness of both Mecp2−/Y rodent models. Conclusions The novel Mecp2−/Y rat model recapitulated numerous RTT-like symptoms as Mecp2−/Y mouse models did, which makes it a valuable alternative model in the RTT studies when the body size matters.
- Subjects :
- 0301 basic medicine
congenital, hereditary, and neonatal diseases and abnormalities
Knockout rat
Cognitive Neuroscience
Rat model
Rett syndrome
Biology
Pathology and Forensic Medicine
MECP2
03 medical and health sciences
0302 clinical medicine
Mecp2-null rat
mental disorders
medicine
Locus coeruleus
MECP2 gene
Genetics
Research
medicine.disease
Phenotype
Human genetics
nervous system diseases
030104 developmental biology
Breathing
Behaviors
Pediatrics, Perinatology and Child Health
Neurology (clinical)
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 18661947
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Neurodevelopmental Disorders
- Accession number :
- edsair.doi.dedup.....539ace26b35641e5a4a4d04355a91524
- Full Text :
- https://doi.org/10.1186/s11689-016-9156-7