Mouse Models for the Study of Telomerase

作者: María A. Blasco , Han-Woong Lee , Michael Rizen , Douglas Hanahan , Ron DePinho

DOI: 10.1002/9780470515433.CH11

关键词: PolymeraseRNATelomerase reverse transcriptaseGenetically modified mouseCancer researchTelomeraseTelomerase RNA componentTelomereBiologyKnockout mouse

摘要: The ends of chromosomes, or telomeres, consist short repeated sequences that are synthesized by a ribonucleoprotein-DNA polymerase called telomerase. RNA component telomerase is essential for enzyme activity. maintenance telomere length has been proposed to be cellular viability and play an important role in senescence immortalization. We interested using the mouse as model system study studied activity expression (mTR) two different transgenic models multistage tumorigenesis: islet cell carcinoma squamous carcinoma. In both tumour models, was detected only late-stage tumours, whereas present at higher than normal levels pre-neoplastic stages increased further tumours. However, did not parallel amounts detected, suggesting regulation does correlate with its component. These results establish direct correlation between progression tumours induction activity, suggest initial upregulation early event. To address during development formation, we have constructed knockout RNA, mTR-/-. mice lines derived from them deficient.

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