title: Instability of CGG repeats in transgenic mice.
abstract: Dynamic mutation resulting in the expansion of CGG repeats in the untranslated region (UTR) of the first exon of the FMR1 gene in humans results in fragile X syndrome. Long stretches of CGG repeats that are known to be highly unstable in humans have so far failed to show similar intergenerational instability in transgenic mice. We generated transgenic lines that show a dramatic increase from 26 to >300 repeats in three generations. One of the salient features of our transgene is the inclusion of the origin of replication of simian virus-40 (SV40), which is known to exclude nucleosomes. Three founder mice in FVB/NJ background show expansion of CGG repeats present in the transgene, supporting a postzygotic mechanism for CGG expansion that is independent of a genomic imprinting effect. We discuss here the results of analyzing one of the lines established.
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Baskaran
authors.forename: Sonal
authors.initials: S
authors.lastname: Datta
authors.forename: Arundhati
authors.initials: A
authors.lastname: Mandal
authors.forename: Neerja
authors.initials: N
authors.lastname: Gulati
authors.forename: Satish
authors.initials: S
authors.lastname: Totey
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Anand
authors.forename: Vani
authors.initials: V
authors.lastname: Brahmachari
mesh_terms: D024509:3' Flanking Region; D024506:5' Flanking Region; D000818:Animals; D005260:Female; D018628:Gene Dosage; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D019076:Transgenes; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*