title: MeCP2 deficiency results in robust Rett-like behavioural and motor deficits in male and female rats.
abstract: 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/yand Mecp2ZFN/+rats were significantly reduced by postnatal day 14 and 21, respectively. Early motor and breathing abnormalities were apparent in Mecp2ZFN/yrats, 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.
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Kelsey C
authors.initials: KC
authors.lastname: Patterson
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Hawkins
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Kara M
authors.initials: KM
authors.lastname: Arps
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Mulkey
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA molsen@uab.edu.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Olsen
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D005260:Female; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012727:Sex Characteristics
chemical_list: C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2