title: Restoring the phenotype of fragile X syndrome: insight from the mouse model.
abstract: A mouse model for the fragile X syndrome, the most common form of inherited mental retardation, was generated a number of years ago. It shows characteristics compatible with the clinical symptoms of human patients. These include pathological changes such as macroorchidism, behavioral problems, and diminished visuo-spatial abilities. To investigate whether the fragile X syndrome is a potentially correctable disorder, several groups attempted to 'rescue' the knockout mutation by introduction of an intact copy of the FMR1 gene in the knockout mouse. Two different types of rescue mice have been created by injection of constructs based on FMR1 cDNA or on FMR1 genomic DNA. Several pathological, behavioral and cognitive function tests were performed on these two different rescue mouse lines to compare their characteristics with those of the knockout and control littermates. Each rescue line resembled the control in some aspects though neither of the 2 lines was a full 'rescue', e.g. resemble the control in all aspects investigated. Thus, rescue of some aspects of the phenotype has been achieved by introduction of FMR1 constructs in the fragile X knockout mice. The results implicate that, even if FMR1 production is cell type specific, the quantity of the FMRP expression is highly critical as overproduction may have a harmful effect.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Gantois
authors.forename: C E
authors.initials: CE
authors.lastname: Bakker
authors.forename: E
authors.initials: E
authors.lastname: Reyniers
authors.forename: R
authors.initials: R
authors.lastname: Willemsen
authors.forename: R
authors.initials: R
authors.lastname: D'Hooge
authors.forename: P P
authors.initials: PP
authors.lastname: De Deyn
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
authors.forename: R F
authors.initials: RF
authors.lastname: Kooy
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D018244:Chromosomes, Artificial, Yeast; D003071:Cognition; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D016601:RNA-Binding Proteins; D013737:Testis / Q000473:pathology
chemical_list: D018076:DNA, Complementary; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse