RGD Reference Report - MeCP2 deficiency results in robust Rett-like behavioural and motor deficits in male and female rats. - Rat Genome Database

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MeCP2 deficiency results in robust Rett-like behavioural and motor deficits in male and female rats.

Authors: Patterson, Kelsey C  Hawkins, Virginia E  Arps, Kara M  Mulkey, Daniel K  Olsen, Michelle L 
Citation: Patterson KC, etal., Hum Mol Genet. 2016 Aug 1;25(15):3303-3320. doi: 10.1093/hmg/ddw179. Epub 2016 Jun 21.
RGD ID: 40924662
Pubmed: PMID:27329765   (View Abstract at PubMed)
PMCID: PMC5179928   (View Article at PubMed Central)
DOI: DOI:10.1093/hmg/ddw179   (Journal Full-text)

Since the identification of MECP2 as the causative gene in the majority of Rett Syndrome (RTT) cases, transgenic mouse models have played a critical role in our understanding of this disease. The use of additional mammalian RTT models offers the promise of further elucidating critical early mechanisms of disease as well as providing new avenues for translational studies. We have identified significant abnormalities in growth as well as motor and behavioural function in a novel zinc-finger nuclease model of RTT utilizing both male and female rats throughout development. Male rats lacking MeCP2 (Mecp2ZFN/y) were noticeably symptomatic as early as postnatal day 21, with most dying by postnatal day 55, while females lacking one copy of Mecp2 (Mecp2ZFN/+) displayed a more protracted disease course. Brain weights of Mecp2ZFN/y and Mecp2ZFN/+ rats were significantly reduced by postnatal day 14 and 21, respectively. Early motor and breathing abnormalities were apparent in Mecp2ZFN/y rats, whereas Mecp2ZFN/+ rats displayed functional irregularities later in development. The large size of this species will provide profound advantages in the identification of early disease mechanisms and the development of appropriately timed therapeutics. The current study establishes a foundational basis for the continued utilization of this rat model in future RTT research.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mecp2Ratabnormal motor coordination/balance  IMP compared to SD wild-typeRGD 
Mecp2em1SageRatabnormal motor coordination/balance  IMP compared to SD wild-typeRGD 
SD-Mecp2em1SageRatabnormal motor coordination/balance  IMP compared to SD wild-typeRGD 
Mecp2Ratabnormal scrotum morphology  IMP compared to SD wild-type maleRGD 
Mecp2em1SageRatabnormal scrotum morphology  IMP compared to SD wild-type maleRGD 
SD-Mecp2em1SageRatabnormal scrotum morphology  IMP compared to SD wild-type maleRGD 
Mecp2Ratdecreased brain weight  IMP compared to SD wild-type RGD 
Mecp2em1SageRatdecreased brain weight  IMP compared to SD wild-type RGD 
SD-Mecp2em1SageRatdecreased brain weight  IMP compared to SD wild-type RGD 
Mecp2Ratdecreased locomotor activity  IMP compared to SD wild-typeRGD 
Mecp2em1SageRatdecreased locomotor activity  IMP compared to SD wild-typeRGD 
SD-Mecp2em1SageRatdecreased locomotor activity  IMP compared to SD wild-typeRGD 
Mecp2Ratdecreased pulmonary respiratory rate sexual_dimorphism IMP compared to SD wild-type male RGD 
Mecp2em1SageRatdecreased pulmonary respiratory rate sexual_dimorphism IMP compared to SD wild-type male RGD 
SD-Mecp2em1SageRatdecreased pulmonary respiratory rate sexual_dimorphism IMP compared to SD wild-type male RGD 
Mecp2Ratincreased body weight sexual_dimorphism IMP compared to SD wild-type female RGD 
Mecp2em1SageRatincreased body weight sexual_dimorphism IMP compared to SD wild-type female RGD 
SD-Mecp2em1SageRatincreased body weight sexual_dimorphism IMP compared to SD wild-type female RGD 
Mecp2Ratincreased pulmonary respiratory rate sexual_dimorphism IMP compared to SD wild-type femaleRGD 
Mecp2em1SageRatincreased pulmonary respiratory rate sexual_dimorphism IMP compared to SD wild-type femaleRGD 
SD-Mecp2em1SageRatincreased pulmonary respiratory rate sexual_dimorphism IMP compared to SD wild-type femaleRGD 
Mecp2Ratlimb grasping  IMP compared to SD wild-typeRGD 
Mecp2em1SageRatlimb grasping  IMP compared to SD wild-typeRGD 
SD-Mecp2em1SageRatlimb grasping penetranceIMP compared to SD wild-typeRGD 
Mecp2Ratmalocclusion sexual_dimorphism IMP compared to female heterozygote mutantRGD 
Mecp2em1SageRatmalocclusion sexual_dimorphism IMP compared to female heterozygote mutantRGD 
SD-Mecp2em1SageRatmalocclusion sexual_dimorphism IMP compared to female heterozygote mutantRGD 
Mecp2Ratpremature death sexual_dimorphism IMP compared to male SD wild-typeRGD 
Mecp2em1SageRatpremature death sexual_dimorphism IMP compared to male SD wild-typeRGD 
SD-Mecp2em1SageRatpremature death sexual_dimorphism IMP compared to male SD wild-typeRGD 
Mecp2Ratprogressive hair loss  IMP compared to SD wild-typeRGD 
Mecp2em1SageRatprogressive hair loss  IMP compared to SD wild-typeRGD 
SD-Mecp2em1SageRatprogressive hair loss  IMP compared to SD wild-typeRGD 
Mecp2Ratrough coat sexual_dimorphism IMP compared to SD wild-type maleRGD 
Mecp2em1SageRatrough coat sexual_dimorphism IMP compared to SD wild-type maleRGD 
SD-Mecp2em1SageRatrough coat sexual_dimorphism IMP compared to SD wild-type maleRGD 
Mecp2Ratshort stride length  IMP compared to SD wild-typeRGD 
Mecp2em1SageRatshort stride length  IMP compared to SD wild-typeRGD 
SD-Mecp2em1SageRatshort stride length  IMP compared to SD wild-typeRGD 
Objects Annotated

Genes (Rattus norvegicus)
Mecp2  (methyl CpG binding protein 2)
Mecp2em1Sage  (methyl CpG binding protein 2; zinc finger nuclease induced mutant 1, Sigma Advanced Genetic Engineering Labs)

Strains
SD-Mecp2em1Sage  (NA)


Additional Information