Figure 5
Figure 5. Long-term induction of TRF1 deletion leads to telomere shortening and significant increased number of short telomeres. (A) Representative image of bone marrow Q-FISH of TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre mice undergoing long-term Cre induction (×63 magnification and ×2 optical zoom). (B) Mean telomere length of TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre mice with (after 7-9 and 13 weeks, respectively) and without long-term Cre induction. Mice without pI-pC–induced Cre expression are represented by dark gray bars and mice undergoing pI-pC injections by light gray bars. Two-sided t test and Student paired t test was used for statistical comparison between TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre subgroups. (C) Telomere length distribution of all measured telomeres in the analyzed TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre animals with and without Cre induction. Red line indicates the mean value calculated in panel B, and dashed lines represent 7.5 and 15 kb. All percentages given in the graph are calculated represent the mean values of the respective 3 or 4 measured mice. (D) Relative telomere length difference between the respective treated and untreated TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre mice. Two-sided t test was used for statistical comparison. (E) Telomere length over time of peripheral blood leukocytes in TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre animals undergoing long-term pI-pC injections. TRF1flox/floxMx1-Cre mice showed significant shorter telomeres after 4 and 8 of Cre induction (both P < .005), but no significant difference was observed before Cre induction (P = .26). Two-sided t test and used for statistical comparison between TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre subgroups. (F) Quantification of the percentage of telomeres < 15 kb of analyzed mice of (B) using BM-Q-FISH and of (E) using HT-Q-FISH. Two-sided t test and used for statistical comparison between TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre subgroups of BM-Q-FISH, 2-sided Mann-Whitney U test was used for comparison between TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre subgroups of HT-Q-FISH. (G) Correlation between measured short telomeres (< 15 kb) of the last blood sample taken and remaining survival time in weeks of the mice. (H) Correlation between telomere length of the last blood sample taken and remaining survival time in weeks of the mice. Pearson correlation was used for statistical analysis.

Long-term induction of TRF1 deletion leads to telomere shortening and significant increased number of short telomeres. (A) Representative image of bone marrow Q-FISH of TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre mice undergoing long-term Cre induction (×63 magnification and ×2 optical zoom). (B) Mean telomere length of TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre mice with (after 7-9 and 13 weeks, respectively) and without long-term Cre induction. Mice without pI-pC–induced Cre expression are represented by dark gray bars and mice undergoing pI-pC injections by light gray bars. Two-sided t test and Student paired t test was used for statistical comparison between TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre subgroups. (C) Telomere length distribution of all measured telomeres in the analyzed TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre animals with and without Cre induction. Red line indicates the mean value calculated in panel B, and dashed lines represent 7.5 and 15 kb. All percentages given in the graph are calculated represent the mean values of the respective 3 or 4 measured mice. (D) Relative telomere length difference between the respective treated and untreated TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre mice. Two-sided t test was used for statistical comparison. (E) Telomere length over time of peripheral blood leukocytes in TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre animals undergoing long-term pI-pC injections. TRF1flox/floxMx1-Cre mice showed significant shorter telomeres after 4 and 8 of Cre induction (both P < .005), but no significant difference was observed before Cre induction (P = .26). Two-sided t test and used for statistical comparison between TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre subgroups. (F) Quantification of the percentage of telomeres < 15 kb of analyzed mice of (B) using BM-Q-FISH and of (E) using HT-Q-FISH. Two-sided t test and used for statistical comparison between TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre subgroups of BM-Q-FISH, 2-sided Mann-Whitney U test was used for comparison between TRF1flox/floxMx1-wt and TRF1flox/floxMx1-Cre subgroups of HT-Q-FISH. (G) Correlation between measured short telomeres (< 15 kb) of the last blood sample taken and remaining survival time in weeks of the mice. (H) Correlation between telomere length of the last blood sample taken and remaining survival time in weeks of the mice. Pearson correlation was used for statistical analysis.

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