title: Age-related length variability of polymorphic CAG repeats.
abstract: Somatic instability of CAG repeats has been associated with the clinical progression of CAG repeat diseases. Aging and DNA repair processes influence the somatic stability of CAG repeat in disease and in mouse models. However, most of the studies have focused on genetically engineered transgenic repeats and little is known about the stability of naturally polymorphic CAG repeats. To study whether age and/or DNA repair activity have an effect on the somatic stability of CAG repeats, we analyzed variations of the length of naturally polymorphic CAG repeats in the striatum of young and aged WT and ogg1 KO mice. Some multiple and long polymorphic CAG repeats were observed to have variable length in the striatum of aged mice. Interestingly, a low level of repeat variability was detected in the CAG repeat located in tbp, the only mouse polymorphic CAG repeat that is associated with a trinucleotide disease in humans, in the striatum of aged mice and not in young mice. We propose that age may have an effect on the somatic stability of polymorphic CAG repeats and that such an effect depends on intrinsic CAG repeat characteristics.
authors.affiliation: Department of Neuroscience, Birdsall Building, Mayo Clinic, 4500 San Pablo Road, 32224 Jacksonville, FL, USA; Department of Biomedical and Pharmaceutical Sciences, University of Montana, 32 Campus Drive, Skaggs Building 280, University of Montana, 59812 Missoula, MT, USA. Electronic address: sanchezcontreras.monica@mayo.edu.
authors.forename: Monica
authors.initials: M
authors.lastname: Sanchez-Contreras
authors.affiliation: Center for Environmental Health Sciences, University of Montana, 59812 Missoula, MT, USA; Center for Structural and Functional Neurosciences, University of Montana, 59812 Missoula, MT, USA. Electronic address: fernando.cardozo@umontana.edu.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cardozo-Pelaez
mesh_terms: D000375:Aging; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D051379:Mice; D018345:Mice, Knockout; D019680:Trinucleotide Repeat Expansion
chemical_list: D004247:DNA; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse