ArticleOncogene2003
Characterization of the abnormal pancreatic development, reduced growth and infertility in Cdk4 mutant mice.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Association between type 2 diabetes and CDKN2A/B: a meta-analysis study.Molecular biology reports · 2012Pooled it
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Review
- Male reproductive phenotypes of genetically altered laboratory mice (Frontiers in veterinary science · 2024Review
- Noncanonical CDK4 signaling rescues diabetes in a mouse model by promoting β cell differentiation.The Journal of clinical investigation · 2023Article
- Suppression of neurotransmission on gonadotropin-releasing hormone neurons in letrozole-induced polycystic ovary syndrome: A mouse model.Frontiers in endocrinology · 2022Article
- Testicular aging, male fertility and beyond.Frontiers in endocrinology · 2022Review
- CDK4: a master regulator of the cell cycle and its role in cancer.Genes & cancer · 2022Review
- Hexachlorobenzene, a pollutant in hypothyroidism and reproductive aberrations: a perceptive transgenerational study.Environmental science and pollution research international · 2021Article
- Emerging Roles for theBiomolecules · 2020Review
- Article
- Diverse roles for CDK-associated activity during spermatogenesis.FEBS letters · 2019Review
- CDC123/CAMK1D gene rs12779790 polymorphism and rs10811661 polymorphism upstream of the CDKN2A/2B gene in women with gestational diabetes.Journal of perinatology : official journal of the California Perinatal Association · 2017Article
- Islet biology, the CDKN2A/B locus and type 2 diabetes risk.Diabetologia · 2016Review
- The cell cycle as a brake for β-cell regeneration from embryonic stem cells.Stem cell research & therapy · 2016Review
- Periodic expression of Kv10.1 driven by pRb/E2F1 contributes to G2/M progression of cancer and non-transformed cells.Cell cycle (Georgetown, Tex.) · 2016Article
- Granulosa Cell-Specific Brca1 Loss Alone or Combined with Trp53 Haploinsufficiency and Transgenic FSH Expression Fails to Induce Ovarian Tumors.Hormones & cancer · 2015Article
- Article
- Article
- Effects of aging on hypothalamic-pituitary-adrenal (HPA) axis activity and reactivity in virgin male and female California mice (Peromyscus californicus).General and comparative endocrinology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Cyclin-dependent kinase 4 (Cdk4) and Cdk6, and later Cdk2, in association with their specific cyclin partners, regulate the G1 to S phase cell cycle transition of mammalian cells by phosphorylation of retinoblastoma (Rb) family proteins. Phosphorylation of Rb results in the release of S-phase specific transcription factors; cell cycle-promoting gene expression, and advancement of the cell cycle. Loss of Cdk4 by homologous-targeted disruption leads to a delay in S-phase entry in serum-stimulated mouse embryo fibroblast (MEF) cultures. Homozygous Cdk4-deficient mice display defects in weight gain, fertility and hypoproliferation of specific endocrine cells of the pituitary and pancreas, the latter of which results in a diabetes-like phenotype. In contrast, inheritance of the p16(Ink4a)-insensitive Cdk4(R24C) mutation leads to spontaneous transformation of MEF cultures in vitro and, in vivo, hyperproliferative disorders that progress to cancer. In this manuscript, we report characterization of the abnormal pancreatic development, reduced growth and infertility in Cdk4 mutant mice. We observe that, whereas Cdk4 is dispensable for early pancreatic development, normal Cdk4 expression is critical for optimal growth of the organism. Also, we observe that loss of Cdk4 may result in insulin insensitivity, implicating an additional role of Cdk4 in beta-cell function, in addition to its role in beta-cell proliferation. Further, we demonstrate that loss of Cdk4 leads to an age-dependent defect in spermatogenesis and disruption in the timing of the estrus cycle. Taken together, our results indicate that the overall defects in growth, fertility and pancreatic development in Cdk4-deficient mice may be a combination of cell-type specific defects and altered glucose metabolism, as a result of defects in postnatal pancreatic development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.