title: A protocol for evaluation of Rett Syndrome symptom improvement by metabolic modulators inMecp2-mutant mice.
abstract: Mouse models recapitulate many symptoms of Rett Syndrome, an X-linked disorder caused by mutations in methyl-CpG-binding protein 2 (MECP2). The study ofMecp2-null male mice has provided insight into pathogenesis of the disorder; most recently, dysregulation of cholesterol and lipid metabolism. Perisymptomatic treatment with statin drugs successfully mitigates the effects of this metabolic syndrome, increases longevity and improves motor function. Described here is a metabolic drug screening protocol and timeline for symptom evaluation inMecp2-mutant mice. Specifically, mice are treated twice weekly with a compound of interest alongside subjective health assessments, bi-weekly body composition measurements and blood chemistries. Throughout treatment, behavioral phenotyping tests are carried out at specific time points. This protocol is highly adaptable to other neurological diseases; however, the time for completion depends on the specific mutant model under study. The protocol highlights the use of several different CPMo protocols to carry out testing in a preclinical model.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Buchovecky
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA.
authors.forename: Misty G
authors.initials: MG
authors.lastname: Hill
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Borkey
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Kyle
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA.
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Justice
keywords: Behavioral Assessment; Cholesterol; Drug Treatment; Lipid; Metabolism; Neurodevelopmental Disorders; Rett Syndrome