A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice?
Fig 3
Loss of MSH6 reduces the frequency of expansions but does not significantly reduce the frequency of large contractions in the sperm of Msh6-/- males.
Small pool PCR was carried out on the sperm of 2-month old males as described in the Materials and Methods. A) Representative GeneMapper profiles for sperm samples analyzed by small-pool PCR showing the original paternal allele and 5 alleles, labeled S1-S5, found in sperm. B) The % of alleles with the loss or gain of different repeat numbers seen in the sperm of Msh6+/+ and Msh6-/- mice. A total of 135 and 173 alleles were examined in the sperm of Msh6+/+ and Msh6-/- mice respectively. The proportion of contractions, expansions and alleles that are the same size as the parental allele are indicated above each graph. Differences between these allele classes were compared for each pair of genotypes using Fisher’s exact test in which each allele class was considered in relation to the sum of the other two allele size classes. The allele classes that are significantly different from Msh6+/+ animals are marked with asterisks (p<0.0001). Note that the proportion of the different allele classes differs from the data shown in Fig 2. This difference is likely due to the differences in the ages of the animals in the two data sets since in males the number of expansions increases with age, although it is also possible that this reflects, in part, the contribution of other cell types that might be present in the sperm sample. Note that, in contrast to what is seen in Msh3-/- animals, the distributions of the contracted alleles for both genotypes significantly deviated from unimodality (Hartigans’ dip test: p < 2.2e-16).