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

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal motor coordination/balance  IMP 40924662; 40924662; 40924662compared to SD wild-typeRGD 
abnormal scrotum morphology  IMP 40924662; 40924662; 40924662compared to SD wild-type maleRGD 
decreased brain weight  IMP 40924662; 40924662; 40924662compared to SD wild-type RGD 
decreased locomotor activity  IMP 40924662; 40924662; 40924662compared to SD wild-typeRGD 
decreased pulmonary respiratory rate sexual_dimorphism IMP 40924662; 40924662; 40924662compared to SD wild-type male RGD 
increased body weight sexual_dimorphism IMP 40924662; 40924662; 40924662compared to SD wild-type female RGD 
increased pulmonary respiratory rate sexual_dimorphism IMP 40924662; 40924662; 40924662compared to SD wild-type femaleRGD 
limb grasping  IMP 40924662; 40924662compared to SD wild-typeRGD 
limb grasping penetranceIMP 40924662compared to SD wild-typeRGD 
malocclusion sexual_dimorphism IMP 40924662; 40924662; 40924662compared to female heterozygote mutantRGD 
premature death sexual_dimorphism IMP 40924662; 40924662; 40924662compared to male SD wild-typeRGD 
progressive hair loss  IMP 40924662; 40924662; 40924662compared to SD wild-typeRGD 
rough coat sexual_dimorphism IMP 40924662; 40924662; 40924662compared to SD wild-type maleRGD 
short stride length  IMP 40924662; 40924662; 40924662compared 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