Figures
Modifying the modifier: polymorphic variants of the mismatch repair protein MSH3 modify disease-causing CAG/CTG repeat expansions.
The mismatch repair protein MSH3 is required to drive disease-causing CAG/CTG repeat expansions in Huntington's disease and myotonic dystrophy mice, contrary to its canonical role of mutation avoidance, making MSH3 the major modifier of repeat instability. In this issue, Tomé and colleagues identify mouse strain-specific variants of Msh3 that modify MSH3 protein levels, which dramatically modify levels of tissue-specific CAG repeat instability, much like a tuning dial modifies the volume of music from a stereo amplifier (as imaged). Since levels of somatic CAG expansions can modulate disease onset, progression, and severity, specific DNA repair gene variants may have prognostic implications.
Image Credit: Christopher E. Pearson and Colin T. Pearson, The Hospital for Sick Children.
Citation: (2013) PLoS Genetics Issue Image | Vol. 9(2) February 2013. PLoS Genet 9(2): ev09.i02. https://doi.org/10.1371/image.pgen.v09.i02
Published: February 28, 2013
Copyright: © 2013 Pearson. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The mismatch repair protein MSH3 is required to drive disease-causing CAG/CTG repeat expansions in Huntington's disease and myotonic dystrophy mice, contrary to its canonical role of mutation avoidance, making MSH3 the major modifier of repeat instability. In this issue, Tomé and colleagues identify mouse strain-specific variants of Msh3 that modify MSH3 protein levels, which dramatically modify levels of tissue-specific CAG repeat instability, much like a tuning dial modifies the volume of music from a stereo amplifier (as imaged). Since levels of somatic CAG expansions can modulate disease onset, progression, and severity, specific DNA repair gene variants may have prognostic implications.
Image Credit: Christopher E. Pearson and Colin T. Pearson, The Hospital for Sick Children.