Telomerase consists of two essential subunits, the template RNA (TR; telomerase RNA) and the catalytic subunit TERT (telomerase reverse transcriptase). Knockout mice with a mTR (mouse TR) deletion have been described and well characterized. However, mice with a mTERT (mouse TERT) deletion have not been reported.

mTERT‐knockout mice have been constructed. The first generation mTERT ^−/− mice were fertile, and did not show any noticeable macroscopic or microscopic phenotypic change. All tissue cells derived from mTERT ^−/− mice that were examined lacked telomerase activity, indicating that mTERT is the only gene encoding the telomerase catalytic subunit. Pulse field gel electrophoresis (PFGE) and nondenaturing in‐gel hybridization analyses showed that mouse telomeric DNA has G‐strand 5′‐overhangs, as demonstrated for human and yeast cells. This telomeric single‐stranded G‐tail was also observed in MEF (mouse embryonic fibroblast) and liver cells derived from mTERT ^−/− mice.

mTERT‐knockout mice show phenotypes that are apparently normal at least during the early generations. This observation is similar to that obtained with the mTR‐knockout mice. The presence of the telomeric G‐strand tails in mTERT ^−/− mice suggests that these telomeric 5′‐overhangs are produced by telomerase‐independent mechanisms, as has been proposed for yeast and human.