EXPERIMENTAL FIGURE 12-11 Mice with a mitochondrial DNA polymerase defective for proofreading exhibit premature aging. A line of “knock-in” mice were prepared by methods discussed in Chapter 6 with an aspartic acid-to-alanine mutation in the gene encoding mitochondrial DNA polymerase (D257A), which inactivated the polymerase’s proofreading function. (a) Wild-type and homozygous mutant mice at 390 days old (13 months). The mutant mouse displays many of the features of an aged mouse (>720 days, or 24 months, of age). (b) Plot of survival versus time of wild-type (+/+), heterozygous (D257A/+), and homozygous (D257A/D257A) mice.

[Part (a) Jeff Miller/University of Wisconsin-Madison. Part (b) data from G. C. Kujoth et al., 2005, Science 309:481.]