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5. Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile X premutation mouse model

Author

Adihe Rachel Lokanga, Karen Usdin, Wei Le, Gloria E. Hoffman, and Ali Entezam

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Flap Endonucleases, DNA repair, DNA damage, Biology, Article, Germline, Mice, chemistry.chemical_compound, Genetics, medicine, Animals, Humans, Allele, Genetics (clinical), Mice, Knockout, Bromates, Deoxyguanosine, medicine.disease, Molecular biology, FMR1, Fragile X syndrome, Disease Models, Animal, chemistry, 8-Hydroxy-2'-Deoxyguanosine, Tandem Repeat Sequences, Fragile X Syndrome, Trinucleotide Repeat Expansion, Trinucleotide repeat expansion, Potassium bromate, DNA Damage
Abstract

Tandem repeat expansion is responsible for the Repeat Expansion Diseases, a group of human genetic disorders that includes Fragile X syndrome (FXS). FXS results from expansion of a premutation (PM) allele having 55-200 CGG.CCG-repeats in the 5' UTR of the FMR1 gene. The mechanism of expansion is unknown. We have treated FX PM mice with potassium bromate (KBrO(3)), a potent DNA oxidizing agent. We then monitored the germline and somatic expansion frequency in the progeny of these animals. We show here that KBrO(3) increased both the level of 8-oxoG in the oocytes of treated animals and the germline expansion frequency. Our data thus suggest that oxidative damage may be a factor that could affect expansion risk in humans.

Published
2010

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