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 testes, late-generation mTerc-/- mice show testicular atrophy and apoptotic depletion of germ cells, with comparable reduction in testes weights and depletion of germ cells in all three Ink4a/Arf genotypes.
“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 <i>Ink4a</i> / <i>Arf</i> tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse (2007) · cites this paper as [32]
Telomerase knock-out (mTERC−/−) mice show generation-dependent telomere shortening, resulting in critically short telomeres and both senescence and apoptosis.
“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
Without telomerase, continued cell division leads to telomere shortening, loss of capping function, and p53 activation.
“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]
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, after successive generations of mTR−/− mice, or in aged mTR−/− organs with high proliferative histories.
“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
The induction of p53 coincides with a dramatic increase in apoptosis and decreased cellularity in the G6 mTR−/− testis.
“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
Loss of telomere function in late-generation (G4 onward) mTR−/− mice adversely affects the morphology and physiology of diverse cell types and organ systems.
“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 G6 mTR−/− p53+/− intercrosses, an unusually high rate of productive mating pairs (11 of 22) was observed compared to G6 mTR−/− p53+/+ matings.
“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 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.
“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
Telomerase knockout mice have short dysfunctional telomeres that severely impair progenitor cell function in actively renewing tissues, causing atrophy and reduced regenerative potential, while quiescent low-turnover tissues such as muscle are unaffected.
“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
Late-generation Terc-deficient mice show some signs of accelerated aging.
“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
Each telomerase component is dispensable for life, and telomerase-knockout mice are remarkably normal.
“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 G5-G6 TERC-/- tissues, cytogenetic evidence shows progressive telomere erosion, including signal-free ends, end-to-end fusions, and anaphase bridging.
“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]
Signalling from short telomeres activates checkpoints that cause either senescence or apoptosis, and sometimes both at once.
“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]
The telomerase-knockout mouse is a valuable model for studying telomere-mediated disease mechanisms because its phenotypes closely match those in humans.
“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]
Tissues with rapid cell turnover are especially sensitive to telomere length.
“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]
Dysfunctional telomeres can also activate p53-dependent apoptosis, since mice bearing dysfunctional telomeres show increased apoptosis in proliferative cells.
“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]
By the sixth generation, increased apoptosis and compromised function were observed in highly proliferative tissues including skin, hematopoietic and reproductive systems.
“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]
By the seventh generation, mTR-deficient mice were no longer able to reproduce.
“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]
By the seventh generation, highly proliferative organ systems like the testis, bone marrow, and spleen appeared abnormal in mTR-deficient mice.
“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]
Mice carrying a homozygous germline deletion of the telomerase RNA component gene (Terc−/−) exhibit critically short telomeres and premature development of age-related pathologies from the second or third generation.
“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]
Telomerase-deficient mice with short telomeres show reduced function of various stem cell compartments including those in the bone marrow and skin.
“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]
Short telomeres result in multiple organismal defects caused by defective tissue regeneration.
“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 stem cell and progenitor cell compartments, 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 stability.
“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]
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BackgroundTelomerase modulates Wnt signalling by association with target gene chromatin
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Short Telomeres and Stem Cell Exhaustion Model Duchenne Muscular Dystrophy in mdx/mTR Mice
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BackgroundResultInfluentialTelomere dysfunction and evolution of intestinal carcinoma in mice and humans
Rudolph, K. L., Millard, M., Bosenberg, M. W., & DePinho, R. A. (2001) · Nature Genetics · doi:10.1038/88871 · Cited by 527 · see citing works
Self-citationTelomeric and extra-telomeric roles for telomerase and the telomere-binding proteins
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Self-citationTelomeres Acquire Embryonic Stem Cell Characteristics in Induced Pluripotent Stem Cells
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“Further evidence for a role of telomerase and telomere length in organ homeostasis comes from the study of telomerase-deficient mice (Terc / mice), which show premature aging and a decreased proliferative potential of adult stem cell populations (Blasco et al., 1997; Lee et al., 1998; Herrera et al., 1999; Samper et a…”
BackgroundSelf-citationHallmarks of senescence in carcinogenesis and cancer therapy
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“Late-generation telomerase-deficient mice show severe proliferative defects leading to immune dysfunction and failure to reproduce (Blasco et al., 1997; Lee et al., 1998; Chin et al., 1999; Rudolph et al., 1999).”
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“This shortening is prevented in the germline and certain stem cells (Lee et al., 1998) by the presence of telomerase.”
BackgroundTelomere Position Effect in Human Cells
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Telomeres, stem cells, senescence, and cancer
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“mTR–/– mice are viable; however, as telomeres shorten and chromosome fusions accumulate with increasing generations, the mTR–/– mice show defects in the reproductive and the hematopoietic system (Blasco et al., 1997; Lee et al., 1998; Rudolph et al., 1999).”
BackgroundInfluentialSelf-citationReplication and protection of telomeres
Verdun, R. E., & Karlseder, J. (2007) · Nature · doi:10.1038/nature05976 · Cited by 463 · see citing works
Effects of Telomerase and Telomere Length on Epidermal Stem Cell Behavior
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“This approach has in fact revealed that cells that normally display high proliferation rates in the wild-type mouse are now at a disadvantage in the late backcrosses (Lee et al. 1998).”
BackgroundInhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery
Rudolph, K. L., Chang, S., Millard, M., Schreiber-Agus, N., & DePinho, R. A. (2000) · Science · doi:10.1126/science.287.5456.1253 · Cited by 424 · see citing works
Self-citationDyskeratosis Congenita and Cancer in Mice Deficient in Ribosomal RNA Modification
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“DNA damage signaling in response to telomere dysfunction induces cell cycle arrest, senescence or apoptosi”
BackgroundSelf-citationMultiple Tumor Suppressor Pathways Negatively Regulate Telomerase
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Conditional telomerase induction causes proliferation of hair follicle stem cells
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Telomeres and cell senescence—size matters not
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“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).”
BackgroundTelomere dysfunction and tumour suppression: the senescence connection
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“In addition to promoting cell cycle arrest, dysfunctional telomeres can also activate p53-dependent apoptosis, as mice bearing dysfunctional telomeres show increased apoptosis in proliferative cell”
BackgroundMechanisms and Regulation of Cellular Senescence
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“Transgenic mouse models without or with inducible telomerase [300,301] allowed establishing a link between short telomeres and the onset of aging phenotypes [300,302,303], progeroid syndromes [304], and chronic inflammatory and degenerative conditions [305,306].”
BackgroundCellular senescence, cancer and aging: the telomere connection
Campisi, J., Kim, S.-H., Lim, C.-S., & Rubio, M. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00160-7 · Cited by 400 · see citing works
DNA damage checkpoints in stem cells, ageing and cancer
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Axis of ageing: telomeres, p53 and mitochondria
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Self-citationTelomerase-Mediated Telomere Addition In Vivo Requires DNA Primase and DNA Polymerases α and δ
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Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing
Wong, K.-K., Maser, R. S., Bachoo, R. M., Menon, J., Carrasco, D. R., Gu, Y., Alt, F. W., & DePinho, R. A. (2003) · Nature · doi:10.1038/nature01385 · Cited by 375 · see citing works
“We examined the impact of Atm deficiency as a function of progressive telomere attrition at both the cellular and whole-organism level in mice doubly null for Atm and the telomerase RNA component ( Terc”
BackgroundSelf-citationGonzález‐Suárez, E., Samper, E., Ramírez, A., Flores, J. M., Martín‐Caballero, J., Jorcano, J. L., & Blasco, M. A. (2001) · The EMBO Journal · doi:10.1093/emboj/20.11.2619 · Cited by 372 · see citing works
“1997; Lee et al., 1998 ), the absence of telomerase activity has a dramatic inhibitory impact on skin tumorigenesis (Gonza ´lez-Sua ´rez et al., 2000), indicating that tumor formation in skin requires telomere maintenance above a threshold length.”
BackgroundSelf-citationShort Dysfunctional Telomeres Impair Tumorigenesis in the INK4aΔ2/3 Cancer-Prone Mouse
Greenberg, R. A., Chin, L., Femino, A., Lee, K.-H., Gottlieb, G. J., Singer, R. H., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80761-8 · Cited by 367 · see citing works
Self-citationEffects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells.
Izbicka, E., Wheelhouse, R. T., Raymond, É., Davidson, K. K., Lawrence, R. A., Sun, D., Windle, B. E., Hurley, L. H., & Hoff, D. D. V. (1999) · PubMed · Cited by 358 · see citing works
Natural and pharmacological regulation of telomerase
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Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis
González-Suárez, E., Samper, E., Flores, J. M., & Blasco, M. A. (2000) · Nature Genetics · doi:10.1038/79089 · Cited by 347 · see citing works
Self-citationTelomeres and age-related disease: how telomere biology informs clinical paradigms
Armanios, M. Y. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66370 · Cited by 346 · see citing works
“Cell type–dependent factors determine whether apoptosis, senescence, or a combined phenotype predominates in response to dysfunctional telomeres (14, 24, 25), although the molecular effectors that discriminate between these pathways are not entirely understood.”
Regulation of human telomerase in homeostasis and disease
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“apoptosis and block proliferation [1].”
A Differentiation Checkpoint Limits Hematopoietic Stem Cell Self-Renewal in Response to DNA Damage
Wang, J., Sun, Q., Morita, Y., Jiang, H., Groß, A., Lechel, A., Hildner, K., Guachalla, L. M., Gompf, A., Hartmann, D., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.040 · Cited by 343 · see citing works
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“These dysfunctional telomeres impair stem cell self-renewal, leading to profound defects in proliferating tissues of telomerase knockout mice (Lee et al., 1998; Allsopp et al., 2003).”
Telomere dysfunction causes alveolar stem cell failure
Alder, J. K., Barkauskas, C. E., Limjunyawong, N., Stanley, S. E., Kembou, F., Tuder, R. M., Hogan, B. L. M., Mitzner, W., & Armanios, M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1504780112 · Cited by 339 · see citing works
“In high-turnover epithelial tissues such as the intestinal tract, telomere dysfunction preferentially induces apoptosis (32, 33, 38).”
BackgroundTelomeres: Cancer to Human Aging
Stewart, S. A., & Weinberg, R. A. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104518 · Cited by 336 · see citing works
“…example, studies have demonstrated that mice lacking functional telomerase are unable to maintain proper tissue homeostasis, particularly in tissues of high cell turnover, such as the bone marrow, skin, liver, and gastrointestinal tract (Herrera et al. 1999, Lee et al. 1998, Rudolph et al. 1999).”
BackgroundStress, cell senescence and organismal ageing
de Magalhães, J. P., & Passos, J. F. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.07.001 · Cited by 316 · see citing works
“This in turn results in critically short telomeres which are responsible for an early onset of senescence and apoptosis (Lee et al., 1998) and reduced regenerative capacity of proliferative”
When stem cells grow old: phenotypes and mechanisms of stem cell aging
Schultz, M. B., & Sinclair, D. A. (2016) · Development · doi:10.1242/dev.130633 · Cited by 331 · see citing works
“Only in the sixth generation is stem cell attrition observed, although a skewed HSC lineage potential phenotype can be observed as early as the fourth generation (Ju et al., 2007; Lee et al., 1998).”
BackgroundAllsopp, R. C., Morin, G. B., DePinho, R., Harley, C. B., & Weissman, I. L. (2003) · Blood · doi:10.1182/blood-2002-07-2334 · Cited by 324 · see citing works
Self-citationMechanisms that Regulate Stem Cell Aging and Life Span
Signer, R. A. J., & Morrison, S. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.01.001 · Cited by 320 · see citing works
“…mice exhibit defects in stem cell function in the forebrain, epidermis, intestinal epithelium, and hematopoietic system through cell-autonomous (Lee et al., 1998; Allsopp et al., 2003; Choudhury et al., 2007; Ferrón et al., 2009; Jaskelioff et al., 2011) and non-cell-autonomous effects on…”
Syndromes of Telomere Shortening
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“Because of the end-replication problem (24,52), telomeres shorten successively with each cell division, and short telomeres activate a p53-dependent checkpoint that leads to apoptosis or senescence (Figure 1) (7,11,20,31,34,40,69).”
BackgroundConstitutive telomerase expression promotes mammary carcinomas in aging mice
Artandi, S. E., Alson, S., Tietze, M. K., Sharpless, N. E., Ye, S., Greenberg, R. A., Castrillon, D. H., Horner, J. W., Weiler, S. R., Carrasco, R. D., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.112515399 · Cited by 317 · see citing works
Self-citationTelomere Length Dynamics and Chromosomal Instability in Cells Derived from Telomerase Null Mice
Hande, M. P., Samper, E., Lansdorp, P., & Blasco, M. A. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.144.4.589 · Cited by 313 · see citing works
“Such variation between littermates could be the basis for the fact that only a percentage of KO-G6 mice show defects associated with telomere loss (Lee et al., 1998; Herrera el al., 1999).”
InfluentialSelf-citationShort Telomeres Limit Tumor Progression In Vivo by Inducing Senescence
Feldser, D. M., & Greider, C. W. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.026 · Cited by 314 · see citing works
Self-citationInvolvement of 14‐3‐3 proteins in nuclear localization of telomerase
Seimiya, H., Sawada, H., Muramatsu, Y., Shimizu, M., Ohko, K., Yamane, K., & Tsuruo, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.11.2652 · Cited by 314 · see citing works
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Self-citationHodes, R. J., Hathcock, K. S., & Weng, N. (2002) · Nature reviews. Immunology · doi:10.1038/nri890 · Cited by 315 · see citing works
“However, the breeding of successive generations of telomerase-deficient mice results in the progressive shortening of telomeres and, eventually (after ∼5–6 generations), both males and females are sterile, apparently owing to replicative failure and the increased apoptosis of germ-line cell”
BackgroundShort Telomeres, even in the Presence of Telomerase, Limit Tissue Renewal Capacity
Hao, L.-Y., Armanios, M., Strong, M. A., Karim, B., Feldser, D. M., Huso, D., & Greider, C. W. (2005) · Cell · doi:10.1016/j.cell.2005.11.020 · Cited by 302 · see citing works
“In mice, the apoptosis leads to loss of germ cells and consequently decreased fertility with each generation (Lee et al., 1998; Hemann et al., 2001b).”
BackgroundSelf-citationTelomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation
Wong, K.-K., Chang, S., Weiler, S. R., Ganesan, S., Chaudhuri, J., Zhu, C., Artandi, S. E., Rudolph, K. L., Gottlieb, G. J., Chin, L., et al. (2000) · Nature Genetics · doi:10.1038/79232 · Cited by 309 · see citing works
“We used the telomerase-deficient mouse, in which telomeres are eroded to a critically short length through serial Terc −/− intercrosses to produce successive generations (G1 Terc −/− through G6 Terc −/− ) of Terc −/− mic”
MethodSelf-citation
- 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
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Agricultural and Biological Sciences › Plant Science › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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