Instability of CGG repeats in transgenic mice.
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.
Baskaran
Sujatha
S
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
Datta
Sonal
S
Mandal
Arundhati
A
Gulati
Neerja
N
Totey
Satish
S
Anand
Rajesh R
RR
Brahmachari
Vani
V
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*