Table 1.

Ribosomal protein mouse mutants model DBA.

Gene	Molecular approach	Whole animal and cellular phenotype	Implications	Ref(s)
Rps19	Knockout allele	Homozygote-early embryonic lethality; Heterozygote-no hematologic or developmental phenotype; normal Rps19 expression	Compensation mechanisms in mice	13, 14
Rps19	Xenograft immunodeficient mice with human DBA cells	Improved engraftment and erythropoiesis in RPS19 rescued marrow	Invokes RPS19 haploinsufficiency in DBA; possible role for gene therapy	22, 23
Rps19	Transgene carrying a pathogenic missense mutation (β-actin promoter)	Ubiquitous expression-embryonic lethal; Inducible expression-growth retardation, anemia, reduced erythroid progenitors and red blood cells, rRNA processing defects	RPS19 missense mutations may act through dominant negative mechanism	7
Rps19	Knockdown in erythroid progenitors (ex vivo)	Impaired proliferation, G1 arrest, induction of p53, decreased Myb and Kit	p53-induced cell cycle arrest results in decreased Kit and impaired erythropoiesis	26
Rps19	ENU-induced missense mutation	Homozygote-early embryonic lethality; Heterozygote-dark skin, white belly spot, growth retardation, mild anemia	Activation of p53 mediates tissue specific phenotypes	16
Rps6	Conditional allele	Liver deletion (2 alleles)-proliferation defect after partial hepatectomy; Ubiquitous deletion (one allele)-embryonic lethality, prolonged cell cycle, increased apoptosis; T-cell deletion (2 alleles)-impaired T-cell development; T-cell deletion (one allele)-decreased T-cell survival, proliferation defect in activated T-cells; Keratinocyte deletion (one allele)-dark skin; Melanocyte deletion (one allele)-light skin	Cell cycle checkpoint responds to defects in ribosome biogenesis; activation of p53 mediates tissue specific phenotypes	15,16, 30, 31
Rpl24	Spontaneous mutation	White spotting, retinal defects, kinked tail, growth retardation; mutant cells have a prolonged cell cycle and a growth disadvantage	Phenotypes are mediated by p53	12, 32
5q deletion (Rps14)	Conditional deletion of ~500kb on 5qsyntenic region (Rps14 and 8 other genes)	Macrocytic anemia, megakaryocyte dysplasia, bone marrow apoptosis, progenitor cell defects	Hematopoietic phenotypes are mediated by p53	33