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IBMFS in zebrafish
Table 4. Comparison of mouse and zebrafish models for inherited bone marrow failure syndromes.
Disease
Phenotype of mouse model
Mouse protein similarity with human protein (%)
RPS19 (99%)
Rps19 KO: embryonic lethal, heterozygous fully compensated
Rps19 with ENU-induced missense mutation: embryonic lethality in homozygous. Heterozygous, mild anemia and growth retardation. L-leucine improved the anemia.
Rps19 deficiency (transgenic line): anemia, leukopenia and bone marrow failure. Loss of p53 rescued the phenotype.91
RPL11 (100%)
Rpl11 KO embryonic lethal. Heterozygous, haploinsufficiency: anemia, decreased erythroid progenitors.92
RPS29 (100%)
N/A
RPL5 (98%)
Rpl5 KO embryonic lethal. Heterozygous fully compensated.96
RPS24 (90%)
Rps24 KO embryonic lethal. Heterozygous fully compensated.91
RPL35 (98%)
N/A
RPL14 (94%)
Conditional deletion of Rps14
(and 8 other genes): anemia, bone marrow apoptosis.91
RPS7 (100%)
Rps7 mutations (RPS7V156G and RPS7Y177S): small size, abnormal skeleton
and eye malformation. No anemia.94
RPL35A (99%)
N/A
RPS27 (100%)
N/A
RPS11 (92%)
N/A
Zebrafish protein with similarity Phenotype zebrafish morphant with human protein (%)
Rps19 (86%)
DBA
rps19 mutants. Erythroid defects, compensated for the loss of one Rps19 allele developmental defect and tp53 activation, fully compensated in heterozygous. Decreased HSCs.30,90
rps19 morphant. Severe anemia and developmentala bnormalities. Dysregulation of delta Np63 and tp53.31
rps11 mutants. Erythroid defects, developmental defects and tp53 activation. Decrease HSCs.30,36,38
rpl11 morphant. Morphological defects in the developing brain, small head and eyes and pericardial edema. Upregulation of tp53 and mdm2.35
Rpl11 (96%)
Rps29 (96%)
rps29 mutant. Severe anemia and increased rps29 morphant. Defects in red blood cell apoptosis. P53 mutations near completely rescued development and an increase in apoptotic cells.45
rps29 morphological and hematopoietic phenotype.93
N/A
N/A
rpl35 mutant very high tumor incidence (100%).37,43
Rpl5 (88%)
rpl5 morphant. Primitive and definitive hematopoiesis affected and morphological abnormalities.
Rps24 (87%)
rps24 morphant. Morphological defects: aplasia in the brain, a bent tail and reduced size. Severe anemia, in a tp53-independent manner.42
Rpl35 (92%)
rpl35a morphants. Morphological defects: aplasia in the brain, a bent tail and reduced size. Severe anemia, in a tp53-independent manner.42
Rpl14 (72%)
rpl14 mutant: high number of tumors (74%)43 rpl14 morphant. Severe anemia45 and morphological abnormalities.98
rps7 mutant. Hematopoietic and developmental defect. High tumor incidence (47%).36,37,43
N/A
N/A
RRps7 (96%)
rps7 morphant. Impaired hematopoiesis and tp53 activation.40
Rpl35a (90%)
rpl35a morphants. Morphological defects: aplasia in the brain, a bent tail and reduced size. Severe anemia, in a tp53-independent manner.42,95
Rps27 (98%)
rps27 morphant. Defective erythropoiesis and morphological abnormalities.99
Rps11 (91%)
rps11 mutants. Erythroid defects and tp53 activation. N/A
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