title: Characterization of the MeCP2R168X knockin mouse model for Rett syndrome.
abstract: Rett syndrome, one of the most common causes of mental retardation in females, is caused by mutations in the X chromosomal gene MECP2. Mice deficient for MeCP2 recapitulate some of the symptoms seen in patients with Rett syndrome. It has been shown that reactivation of silent MECP2 alleles can reverse some of the symptoms in these mice. We have generated a knockin mouse model for translational research that carries the most common nonsense mutation in Rett syndrome, R168X. In this article we describe the phenotype of this mouse model. In male MeCP2(R168X) mice life span was reduced to 12-14 weeks and bodyweight was significantly lower than in wild type littermates. First symptoms including tremor, hind limb clasping and inactivity occurred at age 27 days. At age 6 weeks nest building, rotarod, open-field and elevated plus maze experiments showed impaired motor performance, reduced activity and decreased anxiety-like behavior. Plethysmography at the same time showed apneas and irregular breathing with reduced frequency. Female MeCP2R168X mice showed no significant abnormalities except decreased performance on the rotarod at age 9 months. In conclusion we show that the male MeCP2(R168X) mice have a phenotype similar to that seen in MECP2 knockout mouse models and are therefore well suited for translational research. The female mice, however, have a much milder and less constant phenotype making such research with this mouse model more challenging.
authors.affiliation: University Medical Center Göttingen, Department of Child and Adolescent Health - Division of Neuropediatrics, Göttingen, Germany.
authors.forename: Eike
authors.initials: E
authors.lastname: Wegener
authors.affiliation: University Medical Center Göttingen, Department of Child and Adolescent Health - Division of Neuropediatrics, Göttingen, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Brendel
authors.affiliation: German Center for Neurodegenerative Diseases, Göttingen, Germany; University Medical Center Göttingen, Department for Psychiatry and Psychotherapy, Göttingen, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Swen
authors.initials: S
authors.lastname: Hülsmann
authors.affiliation: University Medical Center Göttingen, Department of Child and Adolescent Health - Division of Neuropediatrics, Göttingen, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Gärtner
authors.affiliation: University Medical Center Göttingen, Department of Child and Adolescent Health - Division of Neuropediatrics, Göttingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Huppke
mesh_terms: D000818:Animals; D018389:Codon, Nonsense; D004195:Disease Models, Animal; D005260:Female; D055879:Gene Knock-In Techniques; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D051379:Mice; D010641:Phenotype; D015518:Rett Syndrome / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D012737:Sex Factors; D057170:Translational Research, Biomedical
chemical_list: D018389:Codon, Nonsense; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2