TY - JOUR
T1 - Genome dynamics in aging mice
AU - Dollé, Martijn E.T.
AU - Vijg, Jan
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Random spontaneous genome rearrangements are difficult to detect in vivo, especially in postmitotic tissues. Using a lacZ-plasmid reporter mouse model, we have previously presented evidence for the accumulation of large genome rearrangements in various tissues, including postmitotic tissues, during aging. These rearrangements, which were found to be organ-specific and to increase with age, have one breakpoint in the lacZ-reporter locus and the second elsewhere in the mouse genome. In this present work, we have used a mouse genome sequence database to physically characterize a total of 49 genome rearrangements in the brain, heart, and liver from young and old mice at two lacZ-plasmid reporter loci. Half of all breakpoints in the mouse genome occurred in chromosomes 3 and 4, each carrying a lacZ-reporter cluster, at distances varying from <100 kb to 66 Mb, indicating intrachromosomal deletions or inversions. The other half of the breakpoints in the mouse genome was found randomly on any of the other chromosomes, indicating translocations. Alternatively, part of the intra- and extrachromosomal events could involve transpositions. Regions of extended homology were not found at the breakpoints. These results lead us to postulate potential mechanisms for the origin of large genome rearrangements in mouse tissues and to predict their possible impact as a potential cause of aging.
AB - Random spontaneous genome rearrangements are difficult to detect in vivo, especially in postmitotic tissues. Using a lacZ-plasmid reporter mouse model, we have previously presented evidence for the accumulation of large genome rearrangements in various tissues, including postmitotic tissues, during aging. These rearrangements, which were found to be organ-specific and to increase with age, have one breakpoint in the lacZ-reporter locus and the second elsewhere in the mouse genome. In this present work, we have used a mouse genome sequence database to physically characterize a total of 49 genome rearrangements in the brain, heart, and liver from young and old mice at two lacZ-plasmid reporter loci. Half of all breakpoints in the mouse genome occurred in chromosomes 3 and 4, each carrying a lacZ-reporter cluster, at distances varying from <100 kb to 66 Mb, indicating intrachromosomal deletions or inversions. The other half of the breakpoints in the mouse genome was found randomly on any of the other chromosomes, indicating translocations. Alternatively, part of the intra- and extrachromosomal events could involve transpositions. Regions of extended homology were not found at the breakpoints. These results lead us to postulate potential mechanisms for the origin of large genome rearrangements in mouse tissues and to predict their possible impact as a potential cause of aging.
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U2 - 10.1101/gr.125502
DO - 10.1101/gr.125502
M3 - Article
C2 - 12421760
AN - SCOPUS:0036851242
VL - 12
SP - 1732
EP - 1738
JO - Genome Research
JF - Genome Research
SN - 1088-9051
IS - 11
ER -