The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Essential role of mouse telomerase in highly proliferative organs
Abstract
We have investigated the role of the enzyme telomerase in highly proliferative organs in successive generations of mice lacking telomerase RNA. Late-generation animals exhibited defective spermatogenesis, with increased programmed cell death (apoptosis) and decreased proliferation in the testis. The proliferative capacity of haematopoietic cells in the bone marrow and spleen was also compromised. These progressively adverse effects coincided with substantial erosion of telomeres (the termini of eukaryotic chromosomes) and fusion and loss of chromosomes. 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.
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In the citing paper
“Similarly, in the testes, we observed the previously reported testicular atrophy and associated apoptotic depletion of germ cells in late-generation mTerc -/ -mice (32), with comparable reduction in testes weights ( P = 0.4131) and depletion of germ cells in all three Ink4a / Arf genotypes (Fig. 1 E ).”
From Ink4a / Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse (2007) · cites this paper as [32]
In the citing paper
“Telomerase knock-out (mTERC−/−) mice which carry a homozygous deletion of the RNA component of telomerase (Blasco et al., 1997) show a generation-dependent telomere shortening, which results in critically short telomeres and both senescence and apoptosis (Lee et al., 1998).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as Lee et al., 1998
In the citing paper
“In the absence of telomerase, continued cell division results in telomere shortening, loss of ‘capping’ function, and p53 activation12-15.”
From Telomere dysfunction induces metabolic and mitochondrial compromise (2011) · cites this paper as [13]
In the citing paper
“Due to the very long telomeres of Mus musculus, critical reduction in telomere length and chromosomal instability is only seen following extensive passage of mTR−/− cells (Niida et al. 1998”
From p53 Deficiency Rescues the Adverse Effects of Telomere Loss and Cooperates with Telomere Dysfunction to Accelerate Carcinogenesis (1999) · cites this paper as Lee et al. 1998
In the citing paper
“This induction of p53 coincides with the dramatic increase in apoptosis (as assessed by TUNEL) and decreased cellularity in the G6 mTR−/− testis (Lee et al. 1998”
From p53 Deficiency Rescues the Adverse Effects of Telomere Loss and Cooperates with Telomere Dysfunction to Accelerate Carcinogenesis (1999) · cites this paper as Lee et al. 1998
In the citing paper
“Loss of telomere function in late-generation (G4 onward) mTR−/− mice has been shown to adversely affect the morphology and physiology of diverse cell types and organ systems (Lee et al. 1998; Rudolph et al. 1999”
From p53 Deficiency Rescues the Adverse Effects of Telomere Loss and Cooperates with Telomere Dysfunction to Accelerate Carcinogenesis (1999) · cites this paper as Lee et al. 1998
In the citing paper
“In the G6 mTR−/− p53+/− intercrosses, we observed an unusually high rate of productive mating pairs (11 of 22 mating pairs) compared to G6 mTR−/− p53+/+ matings (Lee et al. 1998”
From p53 Deficiency Rescues the Adverse Effects of Telomere Loss and Cooperates with Telomere Dysfunction to Accelerate Carcinogenesis (1999) · cites this paper as Lee et al. 1998
In the citing paper
“In mTR−/− mice, a decrease in testis size that correlated with germ cell depletion by histology was first evident in G5 mTR−/− animals and became more prevalent in G6 mTR−/− mice (Lee et al. 1998”
From p53 Deficiency Rescues the Adverse Effects of Telomere Loss and Cooperates with Telomere Dysfunction to Accelerate Carcinogenesis (1999) · cites this paper as Lee et al. 1998
In the citing paper
“In agreement with these findings, studies of telomerase knockout mice revealed short dysfunctional telomeres that profoundly impaired progenitor cell function in actively renewing tissues leading to atrophy and reduced regenerative potential, whereas more quiescent low-turnover tissues such as muscle were unaffected (Allsopp et al., 2003; Lee et al., 1998; Rudolph et al., 1999).”
From Short Telomeres and Stem Cell Exhaustion Model Duchenne Muscular Dystrophy in mdx/mTR Mice (2010) · cites this paper as Lee et al., 1998
In the citing paper
“Of note, late-generation Terc-deficient mice show some signs of accelerated aging (Lee et al., 1998; Rudolph et al., 1999”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Lee et al., 1998
In the citing paper
“Surprisingly, each telomerase component was found to be dispensable for life and these telomerase-knockout mice were remarkably normal (60).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [60]
In the citing paper
“In the G5-G6 TERCÀ/À tissues, there was clear cytogenetic evidence of progressive telomere erosion including 'signal-free' ends, chromosomal end-to-end fusions and anaphase bridging at mitosis (60)(61)(62).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [60]
In the citing paper
“The consequent signalling cascades activate checkpoints that induce either cellular senescence or apoptosis, and in at least some contexts both processes occur simultaneously82,85,91,95.”
From The telomere syndromes (2012) · cites this paper as [85]
In the citing paper
“The telomerase-knockout mouse has provided an important model for understanding telomere-mediated disease mechanisms because there is a remarkable convergence with human disease phenotypes (an overview is shown in Table 2)36,82,84,85,97,99–111.”
From The telomere syndromes (2012) · cites this paper as [85]
In the citing paper
“Although it was initially clear that high-turnover tissues are particularly sensitive to telomere length85,101,112”
From The telomere syndromes (2012) · cites this paper as [85]
In the citing paper
“In addition to promoting cell cycle arrest, dysfunctional telomeres can also activate p53-dependent apoptosis, since mice bearing dysfunctional telomeres show increased apoptosis in proliferative cells31-33.”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [31]
In the citing paper
“By the sixth generation (G6), increased apoptosis and compromised function were observed in highly proliferative tissues including skin, hematopoietic and reproductive systems31, 42-44.”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [31]
In the citing paper
“and the mice were no longer able to reproduce (15).”
From Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death (1999) · cites this paper as [15]
In the citing paper
“by the seventh generation, highly proliferative organ systems like the testis, bone marrow, and spleen appeared abnormal”
From Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death (1999) · cites this paper as [15]
In the citing paper
“In particular, mice carrying a homozygous germline deletion of the telomerase RNA component gene (Terc−/−) exhibit critically short telomeres and a premature development of age-related pathologies from the second or third generation [8, 18–20, 51, 70, 72, 101, 103]”
From Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology (2023) · cites this paper as [70]
In the citing paper
“telomerase-deficient mice with short telomeres show reduced function of various stem cell compartments including those in the bone marrow and skin 58, 60”
From The common biology of cancer and ageing (2007) · cites this paper as [58]
In the citing paper
“the generation and characterization of the telomerase knockout mouse model has been instrumental in demonstrating that short telomeres result in multiple organismal defects caused by defective tissue regeneration 57, 58, 59”
From The common biology of cancer and ageing (2007) · cites this paper as [58]
In the citing paper
“In stem cell and progenitor cell compartments3–5, TERT serves an important role in keeping telomeres sufficiently long and stable to prevent the adverse consequences of dysfunctional telomeres on cell viability and chromosomal stability6–8.”
From Conditional telomerase induction causes proliferation of hair follicle stem cells (2005) · cites this paper as [7]
Citations
Cites
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994) · Science · doi:10.1126/science.7605428 · Cited by 7,091 · cited 1×
“From this crisis period, immortal cells emerge that have reactivated telomerase and maintain stable telomere structure”
BackgroundTelomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
Self-citationExtension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
Greider, C. W., & Blackburn, E. H. (1985) · Cell · doi:10.1016/0092-8674(85)90170-9 · Cited by 3,400
Self-citationTelomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256
The RNA Component of Human Telomerase
Feng, J., Funk, W. D., Wang, S.-S., Weinrich, S. L., Avilion, A. A., Chiu, C.-P., Adams, R. R., Chang, E., Allsopp, R. C., Yu, J., et al. (1995) · Science · doi:10.1126/science.7544491 · Cited by 2,227
Self-citationTelomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108
Self-citationCounter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096
Self-citationMeyerson, M., Counter, C. M., Eaton, E. N., Ellisen, L. W., Steiner, P., Caddle, S. D., Ziaugra, L., Beijersbergen, R. L., Davidoff, M. J., Liu, Q., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80538-3 · Cited by 1,784
Telomere reduction in human colorectal carcinoma and with ageing
Hastie, N. D., Dempster, M., Dunlop, M. G., Thompson, A. M., Green, D. K., & Allshire, R. C. (1990) · Nature · doi:10.1038/346866a0 · Cited by 1,650
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- Erslev, A. J. & Lichtman, M. A. in Hematology 4th edn 37–47 (McGraw-Hill, (1993).
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Items 701–800 of 999
Finnon, P., Silver, A. R., & Bouffler, S. D. (2000) · Carcinogenesis · doi:10.1093/carcin/21.4.573 · Cited by 32
Lobanova, A., She, R., Pieraut, S., Clapp, C., Maximov, A., & Denchi, E. L. (2017) · Genes & Development · doi:10.1101/gad.295402.116 · Cited by 32
“to be detrimental to various dividing nonneuronal cell types (Lee et al. 1998; Chin et al. 1999; Rudolph et al. 1999; Jacobs and de Lange 2004; Celli and de Lange 2005; Zhang et al. 2006; Minty et al. 2008; Martinez et al. 2014).”
BackgroundDegenerative periodontal-diseases and oral osteonecrosis: The role of gene-environment interactions
Baldi, D., Izzotti, A., Bonica, P., Pera, P., & Pulliero, A. (2008) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2008.11.005 · Cited by 31
FANCC suppresses short telomere-initiated telomere sister chromatid exchange
Rhee, D. B., Wang, Y., Mizesko, M. C., Zhou, F., Haneline, L. S., & Liu, Y. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp556 · Cited by 33
Characterization and Fate of Telomerase-expressing Epithelia during Kidney Repair
Song, J., Czerniak, S., Wang, T., Ying, W., Carlone, D. L., Breault, D. T., & Humphreys, B. D. (2011) · Journal of the American Society of Nephrology · doi:10.1681/asn.2011050447 · Cited by 31
Phylogeny of aging and related phenoptotic phenomena
Libertini, G. (2015) · Biochemistry (Moscow) · doi:10.1134/s0006297915120019 · Cited by 31
“12 2015 [178, 180] (in any case, the fitness reduction caused by this alterations should be considered in relation to wild conditions and not in the artificial protected conditions of the laboratory).”
BackgroundLiu, C. C., Ma, D., Yan, T., Fan, X., Poon, Z., Poon, L.-F., Goh, S.-A., Rozen, S., Hwang, W. Y. K., Tergaonkar, V., et al. (2016) · Stem Cells · doi:10.1002/stem.2431 · Cited by 29
Modeling aging and cancer in the telomerase knockout mouse
Chang, S. S. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.08.020 · Cited by 32
Loss of Chromosome 13 in Cultured Human Vascular Endothelial Cells
Zhang, L., Aviv, H., Gardner, J. P., Okuda, K., Patel, S. S., Kimura, M., Bardeguez, A. D., & Aviv, A. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4997 · Cited by 31
Telomerase as a possible target for anticancer therapy
Autexier, C. (1999) · Chemistry & Biology · doi:10.1016/s1074-5521(99)80122-7 · Cited by 30
Short and dysfunctional telomeres sensitize the kidneys to develop fibrosis
Saraswati, S., Martínez, P., Graña-Castro, O., & Blasco, M. A. (2021) · Nature Aging · doi:10.1038/s43587-021-00040-8 · Cited by 28
Self-citationYang, T.-L. B., Chen, Q., Deng, J. T., Jagannathan, G., Tobias, J. W., Schultz, D., Wang, S., Lengner, C. J., Rustgi, A. K., Lynch, J. P., et al. (2017) · Nature Communications · doi:10.1038/ncomms14766 · Cited by 31
Cheng, S., Davis, S., & Sharma, S. (2018) · American Journal of Reproductive Immunology · doi:10.1111/aji.12851 · Cited by 31
Stone, R. C., Aviv, A., & Paus, R. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.12.006 · Cited by 30
Telomerase targeted therapy in cancer and cancer stem cells.
Xu, Y., He, K., & Goldkorn, A. (2011) · PubMed · Cited by 30
Telomere dysfunction in human diseases: the long and short of it!
Carroll, K. A., & Ly, H. (2009) · Europe PMC (PubMed Central) · Cited by 30
Telomeric repeat silencing in germ cells is essential for early development inDrosophila
Morgunova, V., Akulenko, N. V., Radion, E., Olovnikov, I. A., Abramov, Y. A., Olenina, L. V., Shpiz, S., Kopytova, D. V., Georgieva, S. G., & Kalmykova, A. I. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv775 · Cited by 31
“At the same time, loss of the terminal DNA is repaired only in germ and stem cells by the synthesis of tandem telomeric repeats (2,3).”
BackgroundDown-regulation of p21 contributes to apoptosis induced by HPV E6 in human mammary epithelial cells
Fan, X., Liu, Y., & Chen, J. J. (2005) · APOPTOSIS · doi:10.1007/s10495-005-6062-y · Cited by 30
Dual roles of telomere dysfunction in initiation and suppression of tumorigenesis
Cosme‐Blanco, W., & Chang, S. S. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.03.011 · Cited by 31
“Defects in the hematopoietic system were manifested by a marked decline in hematopoietic precursor cell numbers, reduced proliferation of T and B lymphocytes upon mitogenic stimulation and splenic atrophy with a reduction in germinal center function (Lee et al., 1998; Herrera et al., 2000).”
BackgroundTelomere Dysfunction and DNA Damage Checkpoints in Diseases and Cancer of the Gastrointestinal Tract
Rudolph, K. L., Hartmann, D., & Opitz, O. G. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.07.037 · Cited by 32
Individual Telomere Lengths in Chronic Myeloid Leukemia
Samassékou, O., Ntwari, A., Hébert, J., & Yan, J. (2009) · Neoplasia · doi:10.1593/neo.09836 · Cited by 30
“Telomerase is active in germ cells, adult stem cells, activated immune cells, and 90% of cancer cells [1,6].”
BackgroundTelomere biology of the chicken: A model for aging research
Swanberg, S. E., O’Hare, T. H., Robb, E. A., Robinson, C. M., Chang, H., & Delany, M. E. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.04.002 · Cited by 32
Butylidenephthalide Suppresses Human Telomerase Reverse Transcriptase (TERT) in Human Glioblastomas
Lin, P., Lin, S., Chen, Y.-L., Chang, J., Ho, L.-I., Liu, P.-Y., Chang, L.-F., Harn, Y., Chen, S., Sun, L., et al. (2011) · Annals of Surgical Oncology · doi:10.1245/s10434-011-1644-0 · Cited by 30
“Telomerase is pertinent to a cell’s potential for self-renewal and is required for longterm cellular proliferation and survival.(3,4) Because human cells progressively lose telomerase activity, telomere DNA is lost during successive rounds of DNA replication.”
BackgroundBüchler, P., Conejo-Garcia, J. R., Lehmann, G., Müller, M., Emrich, T., Reber, H. A., Büchler, M. W., & Friess, H. (2001) · Pancreas · doi:10.1097/00006676-200105000-00001 · Cited by 30
“Therefore, a growing body of evidence suggests that telomerase activity might be a marker for cell proliferation rather than a marker for cell immortalization and malignancy (39,41).”
BackgroundRaymond, É., Soria, J., lzbicka, E., Boussin, F. D., Hurley, L. H., & Hoff, D. D. V. (2000) · Investigational New Drugs · doi:10.1023/a:1006373812586 · Cited by 31
“Subsequent generations have shown to have shorter telomeres and telomere erosion caused defective spermatogenesis and compromised hematopoietic cell proliferation [ 31 ].”
BackgroundRole of angiotensin II in aging
Yi, W., Chen, F., Zhang, H., Tang, P., Yuan, M., Wen, J., Wang, S., & Cai, Z. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1002138 · Cited by 31
“To a certain degree, some cells, including germ cells (Lee et al., 1998), cancer cells (Singhapol et al.”
BackgroundTelomere length status of somatic cell sheep clones and their offspring
Alexander, B., Coppola, G., Perrault, S. D., Peura, T. T., Betts, D. H., & King, W. A. (2007) · Molecular Reproduction and Development · doi:10.1002/mrd.20735 · Cited by 29
“Whereas, gene ‘‘knockout’’ mice for the telomerase RNA template TERC / (Blasco et al., 1997; Lee et al., 1998) or catalytic component TERT / (Liu et al., 2000), both show progressive loss of telomeric DNA, chromosomal instabilities and proliferation defects in highrenewal organ systems.”
InfluentialOrder of genetic events is critical determinant of aberrations in chromosome count and structure
Fauth, C., O’Hare, M. J., Lederer, G., Jat, P., & Speicher, M. R. (2004) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20051 · Cited by 28
“Various authors have addressed the important role of telomerase activity in maintaining chromosomal stability using the telomerase knockout mouse (Blasco et al., 1997; Lee et al., 1998; Hande et al., 1999; Rudolph et al., 1999; Artandi and DePinho, 2000; Artandi et al., 2000; Hemann et al., 2001; Samper et al., 2001;…”
MethodMorange, M. (2011) · Biological Theory · doi:10.1007/s13752-011-0010-6 · Cited by 32
“The enzyme able to regenerate telomeres is absent from adult cells, but is active in germ cells and in immortal cancer cells (Lee et al. 1998).”
BackgroundTelomere dysfunction: a new player in radiation sensitivity
Genescà, A., Martín, M., Latre, L., Soler, D., Pampalona, J., & Tusell, L. (2006) · BioEssays · doi:10.1002/bies.20501 · Cited by 33
“Aged and late generation animals exhibit awide rangeof defects, including chromosome end fusions, genomic instability and depletion of highly proliferative tissues.((11,46)).”
BackgroundJia, W., Wang, S., Horner, J. W., Wang, N., Wang, H., Gunther, E. J., DePinho, R. A., & Zhu, J. (2011) · The FASEB Journal · doi:10.1096/fj.10-173989 · Cited by 23
“cell development and spermatogenesis (17, 23).”
Self-citationTargeting telomeres and telomerase
Sun, D., & Hurley, L. H. (2001) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(01)40443-5 · Cited by 29
Telomerase in cancer: Clinical applications
Urquidi, V., Tarin, D., & Goodison, S. (1998) · Annals of Medicine · doi:10.3109/07853899809002483 · Cited by 29
Golubovskaya, V., Filatov, L. V., Behe, C. I., Presnell, S. C., Hooth, M. J., Smith, G. J., & Kaufmann, W. K. (1999) · Molecular Carcinogenesis · doi:10.1002/(sici)1098-2744(199903)24:3 · Cited by 29
Essential roles for Pot1b in HSC self-renewal and survival
Wang, Y., Shen, M., & Chang, S. S. (2011) · Blood · doi:10.1182/blood-2011-06-361527 · Cited by 28
Age-Related Changes in Subtelomeric Methylation in the Normal Japanese Population
Maeda, T., Guan, J. Z., Oyama, J.-I., Higuchi, Y., & Makino, N. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/gln057 · Cited by 31
The many types of heterogeneity in replicative senescence
Xu, Z., & Teixeira, M. T. (2019) · Yeast · doi:10.1002/yea.3433 · Cited by 29
Impact of Ovarian Aging in Reproduction: From Telomeres and Mice Models to Ovarian Rejuvenation.
Polonio, A. M., Chico-Sordo, L., Córdova-Oriz, I., Medrano, M., García-Velasco, J. A., & Varela, E. (2020) · PubMed Central · Cited by 28
Japanese medaka: A new vertebrate model for studying telomere and telomerase biology
Au, D. W. T., Mok, H. O. L., Elmore, L. W., & Holt, S. E. (2008) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2008.08.005 · Cited by 28
Genomic stability and physiological assessments of live offspring sired by a bull clone, Starbuck II
Ortegon, H., Betts, D. H., Lin, L., Coppola, G., Perrault, S., Blondin, P., & King, W. A. (2006) · Theriogenology · doi:10.1016/j.theriogenology.2006.09.035 · Cited by 28
“Although abnormal telomere lengths have been shown to increase chromosomal abnormalities and negatively affect cellular proliferation in telomerase knock-out mice [45], the role of telomere length in organismal aging is still unresolved.”
BackgroundFunctional dissection of breast cancer risk-associated TERT promoter variants
Helbig, S., Wockner, L. F., Bouendeu, A., Hille‐Betz, U., McCue, K., French, J. D., Edwards, S. L., Pickett, H. A., Reddel, R. R., Chenevix‐Trench, G., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.18226 · Cited by 27
“When cells bypass senescence and continue to proliferate, telomeres become shortened to a critical length leading to a state of crisis with chromosomal end-to-end-fusion events and genomic instability [11, 12].”
Backgroundvan de Ven, M., Andressoo, J., Holcomb, V. B., Hasty, P., Suh, Y., STEEG, H. V., Garinis, G. A., Hoeijmakers, J. H. J., & Mitchell, J. R. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.011 · Cited by 28
“, 2004), telomere maintenance (Lee et al., 1998), chromosome segregation (Baker et al.”
BackgroundAbate-Shen, C. T., Brown, P. H., Colburn, N. H., Gerner, E. W., Green, J. E., Lipkin, M., Nelson, W. G., & Threadgill, D. W. (2008) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0076 · Cited by 29
“For example, analyses of GEM mice have elucidated critical biological mechanisms of tumorigenesis, including the role of telomere length in disease pathogenesis (10) and, more recently, the role of cellular senescence in tumor suppression in vivo (11).”
BackgroundStem cell factor activates telomerase in mouse mitotic spermatogonia and in primordial germ cells
Dolci, S., Levati, L., Pellegrini, M., Faraoni, I., Graziani, G., Carlo, A. D., & Geremia, R. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.8.1643 · Cited by 28
Ding, Z., Green, A. G., Yang, X., Chernenko, G. A., Tang, S., & Pater, A. (2002) · Experimental Cell Research · doi:10.1006/excr.2001.5412 · Cited by 28
The impact of chromosomal alteration on embryo development
King, W. A., Coppola, G., Alexander, B., Mastromonaco, G. F., Perrault, S., Nino-Soto, M. I., Pinton, A., Joudrey, E. M., & Betts, D. H. (2005) · Theriogenology · doi:10.1016/j.theriogenology.2005.09.031 · Cited by 28
Reproductive aging and telomeres: Are women and men equally affected?
Chico-Sordo, L., Córdova-Oriz, I., Polonio, A. M., S-Mellado, L. S., Medrano, M., García-Velasco, J. A., & Varela, E. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111541 · Cited by 27
Yang, C., Pang, Y., Huang, Y., Ye, F., Chen, X., Gao, Y., Zhang, C., Yao, L., & Gao, J. (2022) · GeroScience · doi:10.1007/s11357-022-00578-4 · Cited by 28
A Novel Bmal1 Mutant Mouse Reveals Essential Roles of the C-Terminal Domain on Circadian Rhythms
Park, N., Kim, H.-D., Cheon, S., Row, H., Lee, J. Y., Han, D.-H., Cho, S., & Kim, K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0138661 · Cited by 24
“The ES cells were injected into blastocystes and chimeric mice were generated as described previously [16].”
MethodTelomere Length and Telomerase Activity in Bovine Pre‐implantation Embryos In Vitro
Gilchrist, G. C., Kurjanowicz, P., Mereilles, F., King, W. A., & LaMarre, J. (2014) · Reproduction in Domestic Animals · doi:10.1111/rda.12449 · Cited by 27
“The importance of telomerase was demonstrated in mice lacking TERC, which suffered progressively decreasing longevity, delayed wound healing and an increase in malignancies (Blasco et al. 1997; Lee et al. 1998; Rudolph et al. 1999).”
BackgroundMale Fertility, Chromosome Abnormalities, and Nuclear Organization
Ioannou, D., & Griffin, D. K. (2010) · Cytogenetic and Genome Research · doi:10.1159/000322060 · Cited by 27
“The importance of telomeres in fertilization has been shown in mice where telomerase knockout disrupts reproductive function [Lee et al., 1998].”
BackgroundPark, S. J., & Bejar, R. L. (2018) · Current Stem Cell Reports · doi:10.1007/s40778-018-0133-9 · Cited by 28
Chromosome variation in the embryos of domestic animals
King, W. A. (2008) · Cytogenetic and Genome Research · doi:10.1159/000118743 · Cited by 28
“One of these involving telomerase knock-out mice, with progressively shorter telomeres in each generation, reached a ‘critical’ level of telomere length in less than 10 generations, displayed increased chromosomal abnormalities, impaired synapsis and recombination during meiosis, aberrant embryo cleavage and eventuall…”
BackgroundTelomere Biology of Human Hematopoietic Stem Cells
Elwood, N. J. (2004) · Cancer Control · doi:10.1177/107327480401100214 · Cited by 26
Naing, C., Aung, K., Lai, P. K., & Mak, J. W. (2017) · BMC Cancer · doi:10.1186/s12885-016-2997-3 · Cited by 27
Floyd, W., Pierpoint, M., Su, C., Patel, R., Luo, L., Deland, K., Wisdom, A. J., Zhu, D., Ma, Y., DeWitt, S. B., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci149310 · Cited by 28
“Persistent telomere breaks can lead to genomic instability, mitotic dysfunction, and cell death (25, 26).”
Essential role for telomerase in chronic myeloid leukemia induced by BCR-ABL in mice
Vicente‐Dueñas, C., Barajas-Diego, M., Romero-Camarero, I., González‐Herrero, I., Flores, T., & Sánchez-Garcı́a, I. (2012) · Oncotarget · doi:10.18632/oncotarget.461 · Cited by 26
“Terc-/- mice show phenotypic abnormalities only after successive generations of terc-/- intrecrosses [4, 5].”
BackgroundDefending the end zone: Studying the players involved in protecting chromosome ends
Chan, S., & Chang, S. S. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.06.016 · Cited by 26
“However, Pot1b / animals show abnormalities in highly proliferative organs, including increased apoptosis in intestines and testes [59], similar to the late generation telomerase knockout mice [65].”
BackgroundSchmelzer, E., & Reid, L. M. (2009) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0b013e32832973fc · Cited by 26
“Induced depression of telomerase in vivo in highly proliferative organs like testis and bone marrow, as well as in cell cultures leads to an increase in apoptosis, decrease in proliferation, as well as loss and fusion of chromosomes (4).”
BackgroundRichards, L. A., Kumari, A., Knezevic, K., Thoms, J. A. I., von Jonquières, G., Napier, C. E., Ali, Z., O’Brien, R., Marks-Bluth, J., Maritz, M. F., et al. (2019) · Haematologica · doi:10.3324/haematol.2018.215699 · Cited by 25
Aging: A cell source limiting factor in tissue engineering
Khorraminejad‐Shirazi, M., Dorvash, M., Estedlal, A., Hoveidaei, A. H., Mazloomrezaei, M., & Mosaddeghi, P. (2019) · World Journal of Stem Cells · doi:10.4252/wjsc.v11.i10.787 · Cited by 28
Telomere Recombination Accelerates Cellular Aging in Saccharomyces cerevisiae
Chen, X., Meng, F., & Zhou, J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000535 · Cited by 25
“Telomerase-deficient mice with critically short telomeres exhibit decreased viability associated with diminished proliferative capacity of B and T cells [57–59].”
Watabe‐Rudolph, M., Begus‐Nahrmann, Y., Lechel, A., Rolyan, H., Scheithauer, M.-O., Rettinger, G., Thal, D. R., & Rudolph, K. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027801 · Cited by 28
“In agreement with this assumption, telomere dysfunction induced atrophy of tissues in G3 mTerc mice predominantly affects organ systems with high rates of cell turnover [28,34].”
BackgroundArmstrong, L., Lako, M., van Herpe, I., Evans, J., Saretzki, G. C., & Hole, N. (2004) · Mechanisms of Development · doi:10.1016/j.mod.2004.07.005 · Cited by 26
“Similar results have been reported by studies of telomerase deficient haematopoietic stem cells which have shown reduced colony forming abilities and long-term repopulating capacity (Samper et al., 2002; Lee et al., 1998).”
Findeisen, H. M., Gizard, F., Zhao, Y., Cohn, D. M., Heywood, E. B., Jones, K. L., Lovett, D. H., Howatt, D. A., Daugherty, A., & Bruemmer, D. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.218545 · Cited by 26
Vertebrate Marine Species as Model Systems for Studying Telomeres and Telomerase
McChesney, P. A., Elmore, L. W., & Holt, S. E. (2005) · Zebrafish · doi:10.1089/zeb.2005.1.349 · Cited by 26
“23 Yet, understanding the importance of telomere erosion in organismal aging in a single generation of animal has proven difficult with the current telomerase knockout models.”
Telomeres and telomerase: targets for cancer chemotherapy?
Perry, P. J., & Kèlland, L. R. (1998) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.8.12.1567 · Cited by 26
Genetic and environmental factors influencing human diseases with telomere dysfunction.
Ly, H. (2009) · PubMed · Cited by 25
Zhou, Q.-G., Wu, H.-Y., Zhou, H., Liu, M.-Y., Lee, H. W., Liu, X., Devkota, S., Ro, E., Zhu, D.-Y., & Suh, H. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.106 · Cited by 25
Self-citationTriethylene tetraamine: a novel telomerase inhibitor
Yin, F., Liu, J., & Peng, X. (2003) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2003.09.004 · Cited by 25
The molecular basis of ageing in stem cells
Tam, W. L., Ang, Y.-S., & Lim, B. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.020 · Cited by 25
“In successive generations of mice lacking telomerase RNA, late-generation animals manifested defective spermatogenesis due to increased apoptosis and reduced proliferation in the testis, as well as reduced proliferative capacity of hematopoietic cells in the bone marrow and spleen (Lee et al., 1998).”
BackgroundThe telomere story or the triumph of an open-minded research
Gilson, É., & Ségal-Bendirdjian, E. (2010) · Biochimie · doi:10.1016/j.biochi.2009.12.014 · Cited by 27
Orren, D. K., & Machwe, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158300 · Cited by 27
“However, creation of more complex WRN-deficient models was spurred by two observations: (1) lab mice have extremely long telomeres (20–50 kb) compared to humans (2–15 kb) and (2) even the TERT (telomerase) knockout mouse did not show phenotypes until the sixth generation [172,173].”
BackgroundPulmonary adenocarcinoma–targeted gene therapy by a cancer- and tissue-specific promoter system
Fukazawa, T., Maeda, Y., Durbin, M. L., Nakai, T., Matsuoka, J., Tanaka, H., Naomoto, Y., & Tanaka, N. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0408 · Cited by 24
Telomeres and Essential Hypertension
Aviv, A. (1999) · American Journal of Hypertension · doi:10.1016/s0895-7061(98)00202-7 · Cited by 24
Getliffe, K. M., Dulaimi, D. A., Martin-Ruiz, C. M., Holder, R. L., von Zglinicki, T., Morris, A. G., & Nwokolo, C. U. (2005) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2005.02311.x · Cited by 24
Mammalian meiotic telomeres: composition and ultrastructure in telomerase-deficient mice
Franco, S., Alsheimer, M., Herrera, E., Benavente, R., & Blasco, M. A. (2002) · European Journal of Cell Biology · doi:10.1078/0171-9335-00259 · Cited by 24
Self-citationTGF-β induces telomerase-dependent pancreatic tumor cell cycle arrest
Cassar, L., Li, H., Jiang, F., & Liu, J. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.02.002 · Cited by 26
Wiemann, S. U., Ande, S., Buer, J., Kamino, K., Manns, M. P., & Rudolph, K. L. (2004) · Oncogene · doi:10.1038/sj.onc.1208308 · Cited by 24
“Studies in telomerase deficient mice (mTERC / ) have given experimental evidence that telomere shortening affects organ homeostasis (Lee et al., 1998) and regenerative capacity during aging (Blasco et al., 1997; Herrera et al., 1999; Rudolph et al., 1999).”
BackgroundTelomere Structure, Replication and Length Maintenance
Muniyappa, K., & Kironmai, K. M. (1998) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409239891204242 · Cited by 23
Telomere, DNA damage, and oxidative stress in stem cell aging
Zhang, J., & Ju, Z. (2010) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.20190 · Cited by 25
A Static Magnetic Field Inhibits the Migration and Telomerase Function of Mouse Breast Cancer Cells
Fan, Z., Hu, P., Xiang, L., Liu, Y., He, R., & Lu, T. (2020) · BioMed Research International · doi:10.1155/2020/7472618 · Cited by 24
“Active telomerase, a reverse transcriptase, can directly increase telomere length [6].”
BackgroundTelomere biology disorders: time for moving towards the clinic?
Batista, L. F. Z., Dokal, I. S., & Parker, R. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.08.001 · Cited by 25
Telomerase Activation in Liver Regeneration and Hepatocarcinogenesis: Dr. Jekyll or Mr. Hyde?
Wege, H., Brümmendorf, T. H., & Brümmendorf, T. H. (2007) · Current Stem Cell Research & Therapy · doi:10.2174/157488807779317062 · Cited by 23
“Along this line, late generation telomerase knockout mice with critically short telomeres show defects in homeostasis of highly proliferative organs [ 35 ].”
BackgroundHuang, Y., Hasegawa, H., Wang, S.-W., Ku, C., Lin, Y., Chiou, S., Hou, M., Wu, D., Tsai, E., Saito, S., et al. (2010) · BioMed Research International · doi:10.1155/2011/569034 · Cited by 24
“In mice, the maintenance of telomere length is important because telomerase deficiency shortens their lifespan and leads to premature aging [88–92].”
Responses to Telomere Erosion in Plants
Amiard, S., Ines, O. D., Gallego, M. E., & White, C. I. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086220 · Cited by 22
Xu, T., He, K., Wang, L., & Goldkorn, A. (2011) · The Prostate · doi:10.1002/pros.21355 · Cited by 23
“Contrary to this model of homogeneous telomerase activation, studies of normal tissue stem cell compartments have demonstrated a unique role for telomerase in stem cell activation [36,37], raising the possibility that perhaps telomerase plays a parallel unique role in so-called cancer progenitor (CPC) or tumor initiat…”
ResultExploiting cellular senescence to treat cancer and circumvent drug resistance
Yan, Q., & Wajapeyee, N. (2010) · Cancer Biology & Therapy · doi:10.4161/cbt.9.3.11166 · Cited by 24
Dysfunctional telomeres and hematological disorders
Fiorini, E., Santoni, A., & Colla, S. (2018) · Differentiation · doi:10.1016/j.diff.2018.01.001 · Cited by 25
“Tissues with high rates of cell turnover, such as those in the skin, in the intestinal crypts and in the hematopoietic system, are particularly vulnerable to defects in telomere maintenance genes (Lee et al., 1998; Rudolph et al., 1999).”
BackgroundDa-Silva, N., Arasaradnam, R. P., Getliffe, K. M., Sung, E., Oo, Y. H., & Nwokolo, C. U. (2010) · Digestive and Liver Disease · doi:10.1016/j.dld.2009.12.005 · Cited by 23
Human short-term repopulating cells have enhanced telomerase reverse transcriptase expression
Järås, M., Edqvist, A., Rebetz, J., Salford, L. G., Widegren, B., & Fan, X. (2006) · Blood · doi:10.1182/blood-2005-09-008904 · Cited by 23
Telomerase and oligodendrocyte differentiation
Caporaso, G. L., & Chao, M. V. (2001) · Journal of Neurobiology · doi:10.1002/neu.1077 · Cited by 24
Telomeres: Dysfunction, Maintenance, Aging and Cancer
Liao, P., Yan, B., Wang, C., & Lei, P. (2023) · Aging and Disease · doi:10.14336/ad.2023.1128 · Cited by 22
“…late-generation TERT-or TERC-null mice as a result of increasing telomere erosion, which contributes to organ atrophy, especially in highly proliferative tissues with high rates of self-renewal, such as the skin, intestinal tract, testis, liver during regeneration, and blood [54,55,57,116,122–131].”
Dystrophic Cardiomyopathy: Complex Pathobiological Processes to Generate Clinical Phenotype
Tsuda, T., & Fitzgerald, K. K. (2017) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd4030014 · Cited by 22
“Telomere shortening occurs during aging and activates senescence and apoptotic programs that compromise the function of organs with high rates of proliferation and turnover [187].”
BackgroundAge-related Cardiac Deterioration: insights from Drosophila
Wessells, R. J. (2006) · Frontiers in bioscience · doi:10.2741/2047 · Cited by 23
Pollicita, M., Muscoli, C., Sgura, A., Biasin, A., Granato, T., Masuelli, L., Mollace, V., Tanzarella, C., Duca, C. D., Rodinò, P., et al. (2009) · BMC Neuroscience · doi:10.1186/1471-2202-10-51 · Cited by 23
“, mice with shortened dysfunctional telomeres demonstrate increased apoptosis in germ cells of the testes and crypt cells of the intestine [16,17].”
Sekulovic, S., Gylfadottir, V., Vulto, I. M., Gasparetto, M., Even, Y., Brookes, C., Smith, C. A., Eaves, C. J., Lansdorp, P. M., Rossi, F. M. V., et al. (2011) · Blood · doi:10.1182/blood-2010-11-319632 · Cited by 23
Kojima, H., Kaita, K., Xu, Z., Ou, J.-H. J., Gong, Y., Zhang, M., & Minuk, G. Y. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(03)00215-0 · Cited by 23
“The significant inhibition of telomerase activity documented in transgenic mice is contrary to the increased activity described in hepatocellular carcinoma tissues [31,32,42,43].”
BackgroundAlternative ends: Telomeres and meiosis
Saint-André, C. D. L. R. (2007) · Biochimie · doi:10.1016/j.biochi.2007.08.010 · Cited by 22
González‐Suárez, E., Goytisolo, F. A., Flores, J. M., & Blasco, M. A. (2003) · PubMed · Cited by 23
Self-citation
Metadata
- Authors
- Lee, H.-W., Blasco, M. A., Gottlieb, G. J., Horner, J. W., Greider, C. W., & DePinho, R. A.
- Affiliations
- Albert Einstein College of Medicine (US)
- Quest Diagnostics (United States) (US)
- Johns Hopkins University (US)
- Venue
- Nature
- Published
- 1998-04
- Volume
- 392
- Issue
- 6676
- Pages
- 569-574
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1612842202
- Cited by
- 1,270
- References
- 40
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 23 · 2023: 24 · 2022: 25 · 2021: 40 · 2020: 25 · 2019: 30 · 2018: 38 · 2017: 26 · 2016: 40 · 2015: 45 · 2014: 31 · 2013: 42 · 2012: 49
- FWCI
- 45.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- telomerase, telomeres, spermatogenesis, apoptosis, cell proliferation, testis, hematopoietic cells, bone marrow, spleen, chromosome fusion, chromosome loss, genome stability, tissue renewal, mice
- MeSH terms
- Animals, Cell Division, Chromosome Banding, Female, Embryonic and Fetal Development, Hematopoiesis, Hematopoietic Stem Cells, Lymphocytes, Male, Mice, Inbred C57BL, Ovary, Testis, Telomere, Apoptosis, Telomerase, Mice
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