Terc

Summary

Gene Symbol: Terc
Description: telomerase RNA component
Alias: mTER, mTR
Species: mouse

Top Publications

  1. Gonzalez Suarez E, Samper E, Flores J, Blasco M. Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis. Nat Genet. 2000;26:114-7 pubmed
    ..Mice deficient for Terc RNA (encoding telomerase) lack telomerase activity, and constitute a model for evaluating the role of telomerase ..
  2. Niida H, Matsumoto T, Satoh H, Shiwa M, Tokutake Y, Furuichi Y, et al. Severe growth defect in mouse cells lacking the telomerase RNA component. Nat Genet. 1998;19:203-6 pubmed
    ..Recently, the telomerase RNA component in human and mouse (TERC and Terc, respectively), a telomerase-associated protein TEP1/TLP1 (refs 6,7) and the human catalytic subunit ..
  3. Liu L, Bailey S, Okuka M, Muñoz P, Li C, Zhou L, et al. Telomere lengthening early in development. Nat Cell Biol. 2007;9:1436-41 pubmed
  4. Sarin K, Cheung P, Gilison D, Lee E, Tennen R, Wang E, et al. Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature. 2005;436:1048-52 pubmed
    ..These data indicate that, in addition to its established role in extending telomeres, TERT can promote proliferation of resting stem cells through a non-canonical pathway. ..
  5. Artandi S, Chang S, Lee S, Alson S, Gottlieb G, Chin L, et al. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature. 2000;406:641-5 pubmed
    ..Our data suggest a model in which telomere dysfunction brought about by continual epithelial renewal during life generates the massive ploidy changes associated with the development of epithelial cancers. ..
  6. Blasco M, Lee H, Hande M, Samper E, Lansdorp P, DePinho R, et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell. 1997;91:25-34 pubmed
    To examine the role of telomerase in normal and neoplastic growth, the telomerase RNA component (mTR) was deleted from the mouse germline. mTR-/- mice lacked detectable telomerase activity yet were viable for the six generations analyzed...
  7. Chin L, Artandi S, Shen Q, Tam A, Lee S, Gottlieb G, et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell. 1999;97:527-38 pubmed
  8. Flores I, Blasco M. A p53-dependent response limits epidermal stem cell functionality and organismal size in mice with short telomeres. PLoS ONE. 2009;4:e4934 pubmed publisher
  9. Lansdorp P. Lessons from mice without telomerase. J Cell Biol. 1997;139:309-12 pubmed

More Information

Publications72

  1. Maser R, WONG K, Sahin E, Xia H, Naylor M, Hedberg H, et al. DNA-dependent protein kinase catalytic subunit is not required for dysfunctional telomere fusion and checkpoint response in the telomerase-deficient mouse. Mol Cell Biol. 2007;27:2253-65 pubmed
  2. Sacco A, Mourkioti F, Tran R, Choi J, Llewellyn M, Kraft P, et al. Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cell. 2010;143:1059-71 pubmed publisher
    ..We report that mdx mice lacking the RNA component of telomerase (mdx/mTR) have shortened telomeres in muscle cells and severe muscular dystrophy that progressively worsens with age...
  3. Schaetzlein S, Kodandaramireddy N, Ju Z, Lechel A, Stepczynska A, Lilli D, et al. Exonuclease-1 deletion impairs DNA damage signaling and prolongs lifespan of telomere-dysfunctional mice. Cell. 2007;130:863-77 pubmed
    ..Together, these studies provide evidence that EXO1 contributes to DNA damage signal induction in mammalian cells, and deletion of Exo1 can prolong survival in the context of telomere dysfunction. ..
  4. Martinez P, Siegl Cachedenier I, Flores J, Blasco M. MSH2 deficiency abolishes the anticancer and pro-aging activity of short telomeres. Aging Cell. 2009;8:2-17 pubmed publisher
    ..In particular, progressively shorter telomeres at successive generations of MSH2(-/-) Terc(-/--) mice did not suppress cancer in these mice, indicating that MSH2 deficiency abolishes the tumor suppressor ..
  5. Jiang H, Schiffer E, Song Z, Wang J, Zurbig P, Thedieck K, et al. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease. Proc Natl Acad Sci U S A. 2008;105:11299-304 pubmed publisher
    ..These results support the concept that telomere dysfunction and DNA damage are interconnected pathways that are activated during human aging and disease. ..
  6. Wong K, Chang S, Weiler S, Ganesan S, Chaudhuri J, Zhu C, et al. Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nat Genet. 2000;26:85-8 pubmed
    ..Here we used the telomerase-deficient mouse, null for the essential telomerase RNA gene (Terc), to assess the role of telomerase and telomere function on the cellular and organismal response to ionizing ..
  7. Schoeftner S, Blasco M. Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol. 2008;10:228-36 pubmed
    ..Our results indicate that TelRNAs are novel components of mammalian telomeres, which are anticipated to be fundamental for understanding telomere biology and telomere-related diseases, such as cancer and ageing. ..
  8. Herrera E, Samper E, Martin Caballero J, Flores J, Lee H, Blasco M. Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J. 1999;18:2950-60 pubmed
    Mice deficient for the mouse telomerase RNA (mTR-/-) and lacking telomerase activity can only be bred for approximately six generations due to decreased male and female fertility and to an increased embryonic lethality associated with a ..
  9. Kuhlow D, Florian S, von Figura G, Weimer S, Schulz N, Petzke K, et al. Telomerase deficiency impairs glucose metabolism and insulin secretion. Aging (Albany NY). 2010;2:650-8 pubmed
    ..We here show that young adult mice which are deficient for the Terc subunit of telomerase exhibit impaired glucose tolerance...
  10. Passos J, Nelson G, Wang C, Richter T, Simillion C, Proctor C, et al. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol Syst Biol. 2010;6:347 pubmed publisher
    ..These ROS in turn replenish short-lived DNA damage foci and maintain an ongoing DDR. We show that this loop is both necessary and sufficient for the stability of growth arrest during the establishment of the senescent phenotype. ..
  11. Satyanarayana A, Wiemann S, Buer J, Lauber J, Dittmar K, Wüstefeld T, et al. Telomere shortening impairs organ regeneration by inhibiting cell cycle re-entry of a subpopulation of cells. EMBO J. 2003;22:4003-13 pubmed
    ..This study provides experimental evidence for the existence of an in vivo process of cellular senescence induced by critical telomere shortening that has functional impact on organ regeneration. ..
  12. Siegl Cachedenier I, Flores I, Klatt P, Blasco M. Telomerase reverses epidermal hair follicle stem cell defects and loss of long-term survival associated with critically short telomeres. J Cell Biol. 2007;179:277-90 pubmed
    ..Additionally, telomerase reintroduction into these mice results in a normal life span by preventing degenerative pathologies in the absence of increased tumorigenesis. ..
  13. Marion R, Strati K, Li H, Tejera A, Schoeftner S, Ortega S, et al. Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell. 2009;4:141-54 pubmed publisher
    ..Together, these results highlight the importance of telomere biology for iPS cell generation and functionality. ..
  14. Armanios M, Alder J, Parry E, Karim B, Strong M, Greider C. Short telomeres are sufficient to cause the degenerative defects associated with aging. Am J Hum Genet. 2009;85:823-32 pubmed publisher
    ..Our findings implicate telomere length as a unique heritable trait that, when short, is sufficient to mediate the degenerative defects of aging, even when telomerase is wild-type. ..
  15. Chamberlain J. Duchenne muscular dystrophy models show their age. Cell. 2010;143:1040-2 pubmed publisher
    ..A new mouse model lacking both dystrophin and telomerase (Sacco et al., 2010) closely mimics the pathological progression of human DMD and shows that muscle stem cell activity is a key determinant of disease severity. ..
  16. Garcia Cao I, García Cao M, Tomás Loba A, Martin Caballero J, Flores J, Klatt P, et al. Increased p53 activity does not accelerate telomere-driven ageing. EMBO Rep. 2006;7:546-52 pubmed
    ..From these observations, we conclude that p53 has an active role in eliminating telomere-damaged cells, and we exclude the possibility of an age-promoting effect of p53 on telomere-driven ageing. ..
  17. Muñoz P, Blanco R, Flores J, Blasco M. XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer. Nat Genet. 2005;37:1063-71 pubmed
    ..Finally, we show that a number of human skin tumors have increased expression of TRF2, further highlighting a role for TRF2 in skin cancer...
  18. Saeed H, Abdallah B, Ditzel N, Catala Lehnen P, Qiu W, Amling M, et al. Telomerase-deficient mice exhibit bone loss owing to defects in osteoblasts and increased osteoclastogenesis by inflammatory microenvironment. J Bone Miner Res. 2011;26:1494-505 pubmed publisher
    ..To study the role of telomere shortening in vivo, we studied the phenotype of telomerase-deficient mice (Terc(-/-))...
  19. Blanco R, Muñoz P, Flores J, Klatt P, Blasco M. Telomerase abrogation dramatically accelerates TRF2-induced epithelial carcinogenesis. Genes Dev. 2007;21:206-20 pubmed
    ..we show that telomerase deficiency dramatically accelerates TRF2-induced epithelial carcinogenesis in K5TRF2/Terc-/- mice, coinciding with increased chromosomal instability and DNA damage...
  20. Yuan X, Ishibashi S, Hatakeyama S, Saito M, Nakayama J, Nikaido R, et al. Presence of telomeric G-strand tails in the telomerase catalytic subunit TERT knockout mice. Genes Cells. 1999;4:563-72 pubmed
    ..Knockout mice with a mTR (mouse TR) deletion have been described and well characterized...
  21. Laud P, Multani A, Bailey S, Wu L, Ma J, Kingsley C, et al. Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway. Genes Dev. 2005;19:2560-70 pubmed
  22. Chang S, Multani A, Cabrera N, Naylor M, Laud P, Lombard D, et al. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet. 2004;36:877-82 pubmed
    ..In late-generation mice null with respect to both Wrn and Terc (encoding the telomerase RNA component), telomere dysfunction elicits a classical Werner-like premature aging ..
  23. Qi L, Strong M, Karim B, Armanios M, Huso D, Greider C. Short telomeres and ataxia-telangiectasia mutated deficiency cooperatively increase telomere dysfunction and suppress tumorigenesis. Cancer Res. 2003;63:8188-96 pubmed
    ..of ataxia-telangiectasia mutated (Atm) in telomere function, we generated Atm and telomerase null mice (Atm(-/-) mTR(-/-) iG6 mice)...
  24. Du X, Shen J, Kugan N, Furth E, Lombard D, Cheung C, et al. Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol Cell Biol. 2004;24:8437-46 pubmed
    ..that Wrn and Blm mutations each accentuate pathology in later-generation mice lacking the telomerase RNA template Terc, including acceleration of phenotypes characteristic of latest-generation Terc mutants...
  25. Flores I, Cayuela M, Blasco M. Effects of telomerase and telomere length on epidermal stem cell behavior. Science. 2005;309:1253-6 pubmed
    ..The effects of telomeres and telomerase on stem cell biology anticipate their role in cancer and aging. ..
  26. Lee H, Blasco M, Gottlieb G, Horner J, Greider C, DePinho R. Essential role of mouse telomerase in highly proliferative organs. Nature. 1998;392:569-74 pubmed
    ..These findings indicate an essential role for telomerase, and hence telomeres, in the maintenance of genomic integrity and in the long-term viability of high-renewal organ systems. ..
  27. Flores I, Canela A, Vera E, Tejera A, Cotsarelis G, Blasco M. The longest telomeres: a general signature of adult stem cell compartments. Genes Dev. 2008;22:654-67 pubmed publisher
  28. WONG K, Maser R, Bachoo R, Menon J, Carrasco D, Gu Y, et al. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature. 2003;421:643-8 pubmed
    ..at both the cellular and whole-organism level in mice doubly null for Atm and the telomerase RNA component (Terc)...
  29. Lee J, Sung Y, Cheong C, Choi Y, Jeon H, Sun W, et al. TERT promotes cellular and organismal survival independently of telomerase activity. Oncogene. 2008;27:3754-60 pubmed publisher
    ..Deletion of the telomerase RNA component (TERC) failed to alter the sensitivity of TERT transgenic MEFs to STS treatment...
  30. Samper E, Fernández P, Eguía R, Martín Rivera L, Bernad A, Blasco M, et al. Long-term repopulating ability of telomerase-deficient murine hematopoietic stem cells. Blood. 2002;99:2767-75 pubmed
  31. Espejel S, Franco S, Sgura A, Gae D, Bailey S, Taccioli G, et al. Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. EMBO J. 2002;21:6275-87 pubmed
    ..Here, by generating mice doubly deficient in DNA-PKcs and telomerase (Terc(-/-)/DNA-PKcs(-/-)), we demonstrate that DNA-PKcs also has a fundamental role in telomere length maintenance...
  32. Leri A, Franco S, Zacheo A, Barlucchi L, Chimenti S, Limana F, et al. Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation. EMBO J. 2003;22:131-9 pubmed
    ..telomere shortening leads to a cardiac phenotype, we studied heart function in the telomerase knockout mouse, Terc-/-. We studied Terc-/- mice at the second, G2, and fifth, G5, generation...
  33. Feldser D, Greider C. Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell. 2007;11:461-9 pubmed
    ..of tumor suppression induced by short telomeres, we crossed mice deficient for the RNA component of telomerase, mTR(-/-), with Emu-myc transgenic mice, an established model of Burkitt's lymphoma...
  34. Greenberg R, Chin L, Femino A, Lee K, Gottlieb G, Singer R, et al. Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse. Cell. 1999;97:515-25 pubmed
    ..dysfunction on tumorigenesis was assessed in successive generations of mice doubly null for the telomerase RNA (mTR) and the INK4a tumor suppressor genes...
  35. Pignolo R, Suda R, McMillan E, Shen J, Lee S, Choi Y, et al. Defects in telomere maintenance molecules impair osteoblast differentiation and promote osteoporosis. Aging Cell. 2008;7:23-31 pubmed
    ..In a model of accelerated aging that combines the Wrn mutation with the shortened telomeres of telomerase (Terc) knockout mice, synthetic defects in proliferative tissues result...
  36. Hande M, Samper E, Lansdorp P, Blasco M. Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice. J Cell Biol. 1999;144:589-601 pubmed
    ..chromosomes 2 and 11) in fibroblasts derived from wild-type mice and from mice lacking the mouse telomerase RNA (mTER) gene using quantitative fluorescence in situ hybridization...
  37. Allsopp R, Morin G, DePinho R, Harley C, Weissman I. Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation. Blood. 2003;102:517-20 pubmed
  38. Feldser D, Strong M, Greider C. Ataxia telangiectasia mutated (Atm) is not required for telomerase-mediated elongation of short telomeres. Proc Natl Acad Sci U S A. 2006;103:2249-51 pubmed
    ..Here we show that Atm is dispensable for elongation of short telomeres by telomerase, suggesting that telomerase recruitment in mammalian cells and in yeast may be regulated differently. ..
  39. Wang H, Chen Q, Lee S, Choi Y, Johnson F, Pignolo R. Impairment of osteoblast differentiation due to proliferation-independent telomere dysfunction in mouse models of accelerated aging. Aging Cell. 2012;11:704-13 pubmed publisher
    ..of disrupted telomere maintenance molecules, including mutants in the Werner helicase (Wrn(-/-) ), telomerase (Terc(-/-) ), and Wrn(-/-) Terc(-/-) double mutants predisposed to accelerated bone loss, we measured telomere ..
  40. Nalapareddy K, Choudhury A, Gompf A, Ju Z, Ravipati S, Leucht T, et al. CHK2-independent induction of telomere dysfunction checkpoints in stem and progenitor cells. EMBO Rep. 2010;11:619-25 pubmed publisher
    ..Together, these results indicate that CHK2 mediates the induction of senescence in fibroblasts, but is dispensable for the induction of telomere dysfunction checkpoints at the stem and progenitor cell level in vivo. ..
  41. Siegl Cachedenier I, Muñoz P, Flores J, Klatt P, Blasco M. Deficient mismatch repair improves organismal fitness and survival of mice with dysfunctional telomeres. Genes Dev. 2007;21:2234-47 pubmed
    ..in response to dysfunctional telomeres by generating mice doubly deficient for telomerase and the PMS2 MMR gene (Terc-/-/PMS2-/- mice)...
  42. Blasco M, Rizen M, Greider C, Hanahan D. Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis. Nat Genet. 1996;12:200-4 pubmed
    ..progression, we examined telomerase activity and expression of the recently cloned mouse telomerase RNA component (mTR) in two different transgenic mouse models of multi-stage tumorigenesis...
  43. Khoo C, Carrasco D, Bosenberg M, Paik J, Depinho R. Ink4a/Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse. Proc Natl Acad Sci U S A. 2007;104:3931-6 pubmed
    ..These observations highlight the importance of genetic context in dictating whether telomere dysfunction promotes or suppresses age-related degenerative conditions as well as the rate of initiation and type of spontaneous cancers. ..
  44. Ferrón S, Mira H, Franco S, Cano Jaimez M, Bellmunt E, Ramirez C, et al. Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells. Development. 2004;131:4059-70 pubmed
  45. Karlseder J, Kachatrian L, Takai H, Mercer K, Hingorani S, Jacks T, et al. Targeted deletion reveals an essential function for the telomere length regulator Trf1. Mol Cell Biol. 2003;23:6533-41 pubmed
    ..These data suggest that murine Trf1 has an essential function that is independent of telomere length regulation. ..
  46. Gonzalez Suarez E, Goytisolo F, Flores J, Blasco M. Telomere dysfunction results in enhanced organismal sensitivity to the alkylating agent N-methyl-N-nitrosourea. Cancer Res. 2003;63:7047-50 pubmed
    Here, we use telomerase-deficient mice, Terc(-/-), to study the impact of telomerase abrogation in response to treatment with the alkylating agent N-Methyl-N-Nitrosourea (MNU), a potent carcinogen in the mouse...
  47. Begus Nahrmann Y, Lechel A, Obenauf A, Nalapareddy K, Peit E, Hoffmann E, et al. p53 deletion impairs clearance of chromosomal-instable stem cells in aging telomere-dysfunctional mice. Nat Genet. 2009;41:1138-43 pubmed publisher
    ..Together, these results provide the first experimental evidence for an organ system in which p53-dependent mechanisms prevent tissue destruction in response to telomere dysfunction by depleting genetically instable stem cells. ..
  48. Wiemann S, Satyanarayana A, Buer J, Kamino K, Manns M, Rudolph K. Contrasting effects of telomere shortening on organ homeostasis, tumor suppression, and survival during chronic liver damage. Oncogene. 2005;24:1501-9 pubmed
  49. Hao L, Armanios M, Strong M, Karim B, Feldser D, Huso D, et al. Short telomeres, even in the presence of telomerase, limit tissue renewal capacity. Cell. 2005;123:1121-31 pubmed
    ..To examine the dosage effect of telomerase, we generated a line of mTR+/- mice on the CAST/EiJ background, which has short telomeres...
  50. Hemann M, Strong M, Hao L, Greider C. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell. 2001;107:67-77 pubmed
    ..To investigate the processes that trigger cellular responses to telomere dysfunction, we crossed mTR-/- G6 mice that have short telomeres with mice heterozygous for telomerase (mTR+/-) that have long telomeres...
  51. Chen J, Opperman K, Greider C. A critical stem-loop structure in the CR4-CR5 domain of mammalian telomerase RNA. Nucleic Acids Res. 2002;30:592-7 pubmed
    ..1 loop, allowed RNA-protein binding but significantly impaired telomerase activity. These data establish the presence of the P6.1 stem-loop and its importance for the assembly and enzymatic activity of the mammalian telomerase complex. ..
  52. Hao L, Strong M, Greider C. Phosphorylation of H2AX at short telomeres in T cells and fibroblasts. J Biol Chem. 2004;279:45148-54 pubmed
    Eukaryotic cells undergo arrest and enter apoptosis in response to short telomeres. T cells from late generation mTR(-/-) mice that lack telomerase show increased apoptosis when stimulated to enter the cell cycle...
  53. Sperka T, Song Z, Morita Y, Nalapareddy K, Guachalla L, Lechel A, et al. Puma and p21 represent cooperating checkpoints limiting self-renewal and chromosomal instability of somatic stem cells in response to telomere dysfunction. Nat Cell Biol. 2011;14:73-9 pubmed publisher
    ..Selective inhibition of Puma-dependent apoptosis can result in temporary improvements in maintenance of telomere-dysfunctional organs...
  54. Song Z, Wang J, Guachalla L, Terszowski G, Rodewald H, Ju Z, et al. Alterations of the systemic environment are the primary cause of impaired B and T lymphopoiesis in telomere-dysfunctional mice. Blood. 2010;115:1481-9 pubmed publisher
    ..Together, these data place alterations in the systemic environment on top of the hierarchy of events limiting lymphopoiesis in response to telomere dysfunction. ..
  55. Espejel S, Franco S, Rodriguez Perales S, Bouffler S, Cigudosa J, Blasco M. Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres. EMBO J. 2002;21:2207-19 pubmed
  56. Rossi D, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman I. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature. 2007;447:725-9 pubmed
    ..These data are consistent with DNA damage accrual being a physiological mechanism of stem cell ageing that may contribute to the diminished capacity of aged tissues to return to homeostasis after exposure to acute stress or injury. ..
  57. Ferron S, Marques Torrejon M, Mira H, Flores I, Taylor K, Blasco M, et al. Telomere shortening in neural stem cells disrupts neuronal differentiation and neuritogenesis. J Neurosci. 2009;29:14394-407 pubmed publisher
  58. Morrish T, Greider C. Short telomeres initiate telomere recombination in primary and tumor cells. PLoS Genet. 2009;5:e1000357 pubmed publisher
    ..for telomere maintenance in mammalian cells, we used primary cells and lymphomas from telomerase-deficient mice (mTR-/- and Emumyc+mTR-/-) and CAST/EiJ mouse embryonic fibroblast cells...
  59. Benetti R, García Cao M, Blasco M. Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nat Genet. 2007;39:243-50 pubmed
    ..Telomerase-deficient Terc(-/-) mice with short telomeres show decreased trimethylation of histone 3 at Lys9 (H3K9) and histone 4 at Lys20 (..
  60. Cosme Blanco W, Shen M, Lazar A, Pathak S, Lozano G, Multani A, et al. Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53-dependent cellular senescence. EMBO Rep. 2007;8:497-503 pubmed
    ..cell-cycle arrest and cellular senescence pathways, to show that spontaneous tumorigenesis is potently repressed in Terc -/- p53 ( R172P ) mice...
  61. Lechel A, Holstege H, Begus Y, Schienke A, Kamino K, Lehmann U, et al. Telomerase deletion limits progression of p53-mutant hepatocellular carcinoma with short telomeres in chronic liver disease. Gastroenterology. 2007;132:1465-75 pubmed
    ..The function of telomerase during in vivo hepatocarcinogenesis has not been studied in this genetic context...
  62. Choudhury A, Ju Z, Djojosubroto M, Schienke A, Lechel A, Schaetzlein S, et al. Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat Genet. 2007;39:99-105 pubmed
    ..This study provides experimental evidence that telomere dysfunction induces p21-dependent checkpoints in vivo that can limit longevity at the organismal level. ..
  63. Blasco M, Funk W, Villeponteau B, Greider C. Functional characterization and developmental regulation of mouse telomerase RNA. Science. 1995;269:1267-70 pubmed
    ..Amounts of telomerase RNA increased in immortal cells derived from primary mouse fibroblasts. RNA was detected in all newborn mouse tissues tested but was decreased during postnatal development. ..