title: Long uninterrupted CGG repeats within the first exon of the human FMR1 gene are not intrinsically unstable in transgenic mice.
abstract: Despite the increasing number of disorders known to result from trinucleotide repeat amplification, the molecular mechanism underlying these dynamic mutations is still unknown. In an attempt to create a mouse model for the CGG repeat instability seen in Fragile X syndrome, we constructed transgenes corresponding to FMR1 premutation alleles. While in humans these alleles would expand to full mutation with almost 100% certainty upon maternal transmission, they remain stable in our transgenic mice. Therefore, the presence of a large number of uninterrupted CGGs is not sufficient to cause instability in mice, even in the context of flanking human FMR1 sequences.
authors.affiliation: Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: C
authors.initials: C
authors.lastname: Lavedan
authors.forename: E
authors.initials: E
authors.lastname: Grabczyk
authors.forename: K
authors.initials: K
authors.lastname: Usdin
authors.forename: R L
authors.initials: RL
authors.lastname: Nussbaum
mesh_terms: D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D005091:Exons / Q000235:genetics; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009841:Oligonucleotides; D016601:RNA-Binding Proteins; D015183:Restriction Mapping; D019076:Transgenes / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*; D014960:X Chromosome
chemical_list: D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D009841:Oligonucleotides; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse