FMR1 Premutation Alleles Research Articles

Long Uninterrupted CGG Repeats within the First Exon of the Human FMR1 Gene Are Not Intrinsically Unstable in Transgenic Mice

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.