EXPRESSION OF MOUSE TELOMERASE REVERSE-TRANSCRIPTASE DURING DEVELOPMENT, DIFFERENTIATION AND PROLIFERATION

We have identified the mouse telomerase reverse transcriptase componen t (mTERT) and demonstrate both substantial sequence homology to the hu man ortholog (hTERT), and the presence of reverse transcriptase and te lomerase specific motifs, Furthermore, we show functional interchangea bility with hTERT in in vitro telomerase reconstitution experiments, a s mTERT produces strong telomerase activity in combination with the hu man telomerase RNA component hTR, The mouse TERT is widely expressed a t low levels in adult tissues, with greatest abundance during embryoge nesis and in adult thymus and intestine, The mTERT component mRNA leve ls were regulated during both differentiation and proliferation, while mTR levels remained constant throughout both processes, Comparison of mTERT and mTR levels to telomerase activity indicates that mTERT expr ession is more tightly linked to the regulation of telomerase activity during these processes than is mTR, In contrast to the situation in h uman cell cultures, mTERT transcript levels are present at readily det ectable levels in primary cultured cells and are not upregulated follo wing crisis, The widespread expression of mTERT in primary cells and m ouse tissues could explain the increased frequency of spontaneous immo rtalization of mouse cells in culture and tumorigenesis in vivo.