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Table 1 A summary of phenotypes observed following deletion of cell cycle regulating genes

From: Promiscuous and lineage-specific roles of cell cycle regulators in haematopoiesis

Gene deletion Expression in haematopoieitc system Haematopoietic system Other phenotypes
Cyclin D1 Unexpressed in the majority of haematopoietic lineages No overt haematopoietic phenotype Developmental neurological abnormalities; hypoplastic retina; impaired Schwann cell regeneration
Cyclin D2 Expression in majority of haematopoietic cell types; absent in small pre-B cells Abnormal B-lymphocytes: impaired proliferation; hypo-responsive to BCR and mitogenic stimulation; impaired CD5 B cell development; immunodeficiency in IgG3 and IgA Sterility in females, cerebellar abnormalities, hypoplastic testes in males; cerebellar abnoralities; reduced susceptability to specifc cancers
Cyclin D3 Expression in majority of haematopoietic cell types Depletion of small pre-B cells; impaired thymic T cell development; impaired maturation of granulocytes in the bone marrow; reduced levels of circulating neutrophil granulocytes Resistant to Notch-driven leukaemias
Cyclin D2; Cyclin D3 Upregulation of cyclin D3 in cyclin D2 null B cells; ubiquitous upregulaion of wild-type cyclin in single deletion embryos As single deletions with severe megaloblastic anemia Embryonic lethal at late developmental stages
CDK2 Expression in majority of haematopoietic cell types No overt haematopoietic phenotype Reduced body size; infertility
CDK4 Expression in majority of haematopoietic cell types No overt haematopoietic phenotype Dwarfism-like phenotype; infertility; hypocellularity in many organs; diabetes
CDK6 Expression in majority of haematopoietic cell types Mild haematopoietic defects: hypoplasia of thymuses and spleens; delayed G1 progression in lymphocytes; depletion of megakaryocytes and erythrocytes No overt phenotype
CDK2; CDK4 As above Severe haematopoietic defects: reduced proliferation of multipotential progenitors; decrease in cellularity of all haematopoietic subpopulations Embryonic lethality due to heart defects
CDK4; CDK6 As above Multi-lineage haematopoietic abnormalities: reduction in cellularity of lymphoid, myeloid and granulocyte-macrophage progenitors; loss of mature haematopoietic cells Late-stage embryonic lethal; anaemia
p15INK4b Absent in HSC; increases in myeloid and lymphoid lineages No overt haematopoietic phenotype No overt phenotype
p16INK4a Highly expressed in HSC; down-regulated with differentiation of all lineages No overt haematopoietic phenotype; increased ability for clonal expansion of haematopoetic progenitor cells; long latency B-cell lymphomas No overt phenotype
p18INK4c Higher levels in HSC compared with more mature myeloid and lymphoid cells Hyperplastic spleen and thymus; increased cellularity and hypersensitivity of T and B-cell lymphocytes to mitogenic stimulation; T-cell lymphoma Widespread hyperplasia and organomegaly
p19INK4d Higher levels in HSC compared with more mature myeloid and lymphoid cells No overt haematopoietic phenotype No overt phenotype
p21Cip1 Variable Increase in HSC cycling; reduced progenitor cell replication; decrease of circulating inflammatory monocytes in peripheral blood No overt phenotype
p27Kip1 Variable Increased progenitor cell activity; hyperplasia observed in most haematopoietic organs, particularly pronounced in the thymus and spleen Multiple organ hyperplasia
p57Kip2 Induced by TGF-β in specific progenitor/HSC (CB-CD34) No overt haematopoietic phenotype No overt phenotype
  1. HSC; haematopoeitic stem cells, CDK; cyclin-dependent kinase.