Mice lacking cyclin D1 are small and show defects in eye and mammary gland development.
Open accessAbstract
Using homologous recombination, mice lacking cyclin D1 were generated by replacing most of the first exon of the Cyl-1 gene with sequences encoding neomycin resistance. Cyl-1(-1-) mice were viable and fertile but consistently smaller than their heterozygous or wild-type littermates. The nullizygous animals also showed two distinctive abnormalities: a severe retinopathy caused by impaired development of all layers of the retina and, in the mammary gland during pregnancy, a marked reduction in acinar development accompanied by a failure to lactate. Approximately 50% of animals also had a malformation of the jaw that manifested itself as a misalignment of the incisor teeth. Mouse embryo fibroblasts isolated from 14 day nullizygous, heterozygous, or wild-type embryos and grown under standard conditions showed similar cell-cycle and growth characteristics. Thus although cyclin D1 kinase activity may facilitate G1 progression, it is not essential for the development of most tissues and organs, and only a few specialized cell lineages are demonstrably sensitive to its absence.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Other D type cyclins can functionally replace cyclin D1 in most tissues.
“From experiments with cyclin D1 KO mice, it is known that other D type cyclins can functionally replace cyclin D1 in most tissues.17,18”
From Interleukin 6 Is Important for Survival After Partial Hepatectomy in Mice (2003) · cites this paper as [18]
The Discussion (page not provided) proposes that D-type cyclins might substitute for one another, but also offers alternative signaling pathways as an explanation and says further experiments are needed to distinguish them. It therefore does not establish that other D-type cyclins functionally replace cyclin D1 in most tissues. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The retinoblastoma protein and cell cycle control
Weinberg, R. A. (1995) · Cell · doi:10.1016/0092-8674(95)90385-2 · Cited by 4,862 · see citing works
DeCaprio, J. A., Ludlow, J. W., Lynch, D., Furukawa, Y., Griffin, J., Piwnica-Worms, H., Huang, C.-M., & Livingston, D. M. (1989) · Cell · doi:10.1016/0092-8674(89)90507-2 · Cited by 897 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Ando, K., F. Ajchenbaumcymbalista, and J. Griffin. 1993. Reg- ulation of Gi/S transition by cyclin-D2 and cyclin-D3 in hematopoietic-cells. Proc. Natl. Acad. Sci. 90: 9571-9575.
- Bradley, A. 1987. Production and analysis of chimeric mice. In Teratocarcinomas and embryonic stem cells: A practical approach (ed. E.J. Robertson), pp. 113-151. IRL Press, Ox- ford, UK.
- Robertson, E.J. 1987. Embryo-derived stem cell lines. In Tera- tocarcinomas and embryonic stem cells: A practical ap- proach (ed. E.J. Robertson), pp. 71-112. IRL Press, Oxford, UK.
Cited by
Sorted by citations
CDK inhibitors: positive and negative regulators of G1-phase progression
Sherr, C. J., & Roberts, J. M. (1999) · Genes & Development · doi:10.1101/gad.13.12.1501 · Cited by 6,115 · see citing works
Sherr, C. J. (1996) · Science · doi:10.1126/science.274.5293.1672 · Cited by 5,379 · see citing works
The RB and p53 pathways in cancer
Sherr, C. J., & McCormick, F. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00102-2 · Cited by 1,690 · see citing works
Cheng, M., Olivier, P., Diehl, J. A., Fero, M., Roussel, M. F., Roberts, J. M., & Sherr, C. J. (1999) · The EMBO Journal · doi:10.1093/emboj/18.6.1571 · Cited by 1,142 · see citing works
Living with or without cyclins and cyclin-dependent kinases
Sherr, C. J., & Roberts, J. M. (2004) · Genes & Development · doi:10.1101/gad.1256504 · Cited by 1,089 · see citing works
Specific protection against breast cancers by cyclin D1 ablation
Yu, Q., Geng, Y., & Sicinski, P. (2001) · Nature · doi:10.1038/35082500 · Cited by 934 · see citing works
Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6
Malumbres, M., Sotillo, R., Santamarı́a, D., Galán, J., Cerezo, A., Ortega, S., Dubus, P., & Barbacid, M. (2004) · Cell · doi:10.1016/j.cell.2004.08.002 · Cited by 793 · see citing works
CDK-Independent Activation of Estrogen Receptor by Cyclin D1
Zwijsen, R. M. L., Wientjens, E., Klompmaker, R., van der Sman, J., Bernards, R., & Michalides, R. J. A. M. (1997) · Cell · doi:10.1016/s0092-8674(00)81879-6 · Cited by 720 · see citing works
Mouse development and cell proliferation in the absence of D-cyclins
Kozar, K., Ciemerych, M. A., Rebel, V. I., Shigematsu, H., Zagozdzon, A., Sicinska, E., Geng, Y., Yu, Q., Bhattacharya, S., Bronson, R. T., et al. (2004) · Cell · doi:10.1016/j.cell.2004.07.025 · Cited by 647 · see citing works
Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases
Hydbring, P., Malumbres, M., & Sicinski, P. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.27 · Cited by 528 · see citing works
Requirement for CDK4 kinase function in breast cancer
Yu, Q., Sicinska, E., Geng, Y., Ahnström, M., Zagozdzon, A., Kong, Y., Gardner, H., Kiyokawa, H., Harris, L. N., Stål, O., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2005.12.012 · Cited by 429 · see citing works
Targeted Disruption of CDK4 Delays Cell Cycle Entry with Enhanced p27 <sup>Kip1</sup> Activity
Tsutsui, T., Hesabi, B., Moons, D. S., Pandolfi, P. P., Hansel, K. S., Koff, A., & Kiyokawa, H. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.10.7011 · Cited by 395 · see citing works
The Requirement for Cyclin D Function in Tumor Maintenance
Choi, Y. J., Li, X., Hydbring, P., Sanda, T., Stefano, J., Christie, A. L., Signoretti, S., Look, A. T., Kung, A. L., von Boehmer, H., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.09.015 · Cited by 342 · see citing works
Cyclins D2 and D1 Are Essential for Postnatal Pancreatic β-Cell Growth
Kushner, J. A., Ciemerych, M. A., Sicinska, E., Wartschow, L. M., Teta, M., Long, S. Y., Sicinski, P., & White, M. F. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.9.3752-3762.2005 · Cited by 334 · see citing works
Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis
Landis, M. W., Pawlyk, B. S., Li, T., Sicinski, P., & Hinds, P. W. (2006) · Cancer Cell · doi:10.1016/j.ccr.2005.12.019 · Cited by 329 · see citing works
Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen
Bienvenu, F., Jirawatnotai, S., Elias, J. E., Meyer, C. A., Mizeracka, K., Marson, A., Frampton, G. M., Cole, M. F., Odom, D. T., Odajima, J., et al. (2010) · Nature · doi:10.1038/nature08684 · Cited by 276 · see citing works
Development of mice expressing a single D-type cyclin
Ciemerych, M. A., Kenney, A. M., Sicinska, E., Kalaszczynska, I., Bronson, R. T., Rowitch, D. H., Gardner, H., & Sicinski, P. (2002) · Genes & Development · doi:10.1101/gad.1023602 · Cited by 267 · see citing works
Wu, H., Wade, M., Krall, L., Grisham, J., Xiong, Y., & Van Dyke, T. (1996) · Genes & Development · doi:10.1101/gad.10.3.245 · Cited by 234 · see citing works
Cell type-specific effects of <i>Rb</i> deletion in the murine retina
MacPherson, D., Sage, J., Kim, T., Ho, D., McLaughlin, M. E., & Jacks, T. (2004) · Genes & Development · doi:10.1101/gad.1203304 · Cited by 222 · see citing works
Wide spectrum of tumors in knock‐in mice carrying a Cdk4 protein insensitive to INK4 inhibitors
Sotillo, R., Dubus, P., Martn, J., de la Cueva, E., Ortega, S., Malumbres, M., & Barbacid, M. (2001) · The EMBO Journal · doi:10.1093/emboj/20.23.6637 · Cited by 208 · see citing works
β-Catenin and Tcfs in Mammary Development and Cancer
Hatsell, S., Rowlands, T., Hiremath, M., & Cowin, P. (2003) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1023/a:1025944723047 · Cited by 209 · see citing works
Interleukin 6 Is Important for Survival After Partial Hepatectomy in Mice
Blindenbacher, A., Wang, X., Langer, I., Savino, R., Terracciano, L., & Heim, M. H. (2003) · Hepatology · doi:10.1053/jhep.2003.50378 · Cited by 202 · see citing works
Pestell, R. G. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.03.001 · Cited by 197 · see citing works
Cell Death in Chondrocytes, Osteoblasts, and Osteocytes
Komori, T. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122045 · Cited by 176 · see citing works
“In the growth plate, Cyclin D1 is strongly expressed in the proliferating layer [15], and Cyclin D1-deficient mice show dwarfism with a diminished proliferating layer in the growth plate [13,15,17,18].”
BackgroundEpner, E., Reik, A., Cimbora, D., Telling, A., Bender, M. A., Fiering, S., Enver, T., Martin, D. I. K., Kennedy, M., Keller, G., et al. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80144-6 · Cited by 183 · see citing works
Bridged Proteolysis Targeting Chimera (PROTAC) Enables Degradation of Undruggable Targets
Xiong, Y., Zhong, Y., Yim, H., Yang, X., Park, K.-S., Xie, L., Poulikakos, P. I., Han, X., Xiong, Y., Chen, X., et al. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c09255 · Cited by 154 · see citing works
Martín, J., Hunt, S. L., Dubus, P., Sotillo, R., Néhmé-Pélluard, F., Magnuson, M. A., Parlow, A. F., Malumbres, M., Ortega, S., & Barbacid, M. (2003) · Oncogene · doi:10.1038/sj.onc.1206506 · Cited by 122 · see citing works
Friedrichsen, B. N., Richter, H. E., Hansen, J. A., Rhodes, C. J., Nielsen, J. H., Billestrup, N., & Møldrup, A. (2003) · Molecular Endocrinology · doi:10.1210/me.2002-0356 · Cited by 93 · see citing works
Early Embryonic Death in Mice Lacking the β-Catenin-Binding Protein Duplin
Nishiyama, M., Nakayama, K., Tsunematsu, R., Tsukiyama, T., Kikuchi, A., & Nakayama, K. I. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.19.8386-8394.2004 · Cited by 86 · see citing works
Sicinska, E., Lee, Y.-M., Gits, J., Shigematsu, H., Yu, Q., Rebel, V. I., Geng, Y., Marshall, C. J., Akashi, K., Dorfman, D. M., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00800-06 · Cited by 45 · see citing works
- Authors
- Fantl, V, Stamp, G., Andrews, A., Rosewell, I., & Dickson, C.
- Affiliations
- Hammersmith Hospital (GB)
- ORCID
- Stamp, G
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1995-10-01
- Volume
- 9
- Issue
- 19
- Pages
- 2364-2372
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2004391147
- Cited by
- 691
- References
- 2
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 19 · 2023: 12 · 2022: 9 · 2021: 7 · 2020: 10 · 2019: 7 · 2018: 9 · 2017: 7 · 2016: 18 · 2015: 7 · 2014: 13 · 2013: 24 · 2012: 20
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- cyclin D1, retinopathy, eye development, mammary gland development, lactation failure, jaw malformation, cell cycle, tissue growth, mouse embryonic fibroblasts
- MeSH terms
- Animals, Base Sequence, Body Constitution, Cell Cycle, Cell Differentiation, Cells, Cultured, Female, Fibroblasts, Heterozygote, Homozygote, Jaw Abnormalities, Mammary Glands, Animal, Mice, Transgenic, Molecular Sequence Data, Pregnancy, Recombination, Genetic, Retina, Stem Cells, Oncogene Proteins, Gene Expression, Cyclins, DNA Primers, Gene Targeting, Cyclin D1, 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 ›
Are you an author, or do you see a problem with this page? Request a review
