Phenotypes associated with this allele

• Allele Symbol: Rnh1^tm1Rall
• Allele Name: targeted mutation 1, Ramanjaneyulu Allam
• Allele ID: MGI:6162065
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rnh1^tm1Rall/Rnh1^tm1Rall	involves: 129S/SvEv * C57BL/6	MGI:6276583
ht2	Rnh1^tm1Rall/Rnh1^+	involves: 129S/SvEv * C57BL/6	MGI:6276584

Genotype
MGI:6276583

hm1

• Allelic Composition: Rnh1^tm1Rall/Rnh1^tm1Rall
• Genetic Background: involves: 129S/SvEv * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

embryonic lethality, complete penetrance ( J:261784 )

• homozygous embryos die from anemia between E8.5 and E10, with no viable embryos detected after E10.5

embryo

embryonic growth retardation ( J:261784 )

• overall growth retardation between E8.5 and E10

• however, embryos develop normally before E7.25

abnormal visceral yolk sac blood island morphology ( J:261784 )

• severe reduction of nucleated erythroid cells in yolk sac blood islands at E10

• however, endothelium-lined blood vessels appear unaffected

pale yolk sac ( J:261784 )

• severe reduction in blood levels in the yolk sac; the few erythroid cells found in yolk sac blood islands show reduced benzidine staining, indicating decreased hemoglobin load

abnormal embryonic erythropoiesis ( J:261784 )

• severe reduction of erythroid cells in yolk sac blood islands and in the placenta at E10

• however, blood vessel formation and generation of hematopoietic stem/progenitor cells (HSPCs) are normal at E9.5

growth/size/body

embryonic growth retardation ( J:261784 )

• overall growth retardation between E8.5 and E10

• however, embryos develop normally before E7.25

hematopoietic system

anemia ( J:261784 )

• severe reduction in blood levels in the yolk sac and in the embryo proper

abnormal erythroid progenitor cell morphology ( J:261784 )

• in a methylcellulose colony-forming assay, erythroid colonies derived from E8.5 yolk sac cells appear pale in color and contain less mature erythroid cells than control yolk sac colonies

decreased erythroid progenitor cell number ( J:261784 )

• in a methylcellulose colony-forming assay, the number of erythroid colonies derived from E8.5 yolk sac cells is significantly decreased relative to control yolk sac colonies

• FACS analysis of colony cells showed that Ter119+ CD71+ erythroid cells develop at a significantly lower frequency than in control colonies

• transient expression of GATA1 in yolk sac cells restores the frequency of erythroid colonies to normal levels

abnormal erythroblast morphology ( J:261784 )

• significantly higher % of binucleated erythroblasts in the yolk sac, indicating ineffective erythropoiesis

abnormal embryonic erythrocyte morphology ( J:261784 )

• embryonic-primitive erythroid (Ter119+ and CD71+) cells are significantly decreased in the yolk sac at E8.5 and E9.5

• however, the % of hematopoietic stem/progenitor cells (c-Kit+CD41+ HSPCs) present in the yolk sac is normal

abnormal embryonic erythropoiesis ( J:261784 )

• severe reduction of erythroid cells in yolk sac blood islands and in the placenta at E10

• however, blood vessel formation and generation of hematopoietic stem/progenitor cells (HSPCs) are normal at E9.5

homeostasis/metabolism

abnormal translation ( J:261784 )

• although mRNA levels of Gata1 (an erythroid transcription factor) are relatively normal, GATA1 protein levels are decreased, suggesting that GATA1 translation is impaired

cellular

abnormal translation ( J:261784 )

• although mRNA levels of Gata1 (an erythroid transcription factor) are relatively normal, GATA1 protein levels are decreased, suggesting that GATA1 translation is impaired

Genotype
MGI:6276584

ht2

• Allelic Composition: Rnh1^tm1Rall/Rnh1⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6

hematopoietic system

abnormal erythropoiesis ( J:261784 )

• adult heterozygotes show reduced splenic erythropoiesis; all 4 erythroid subpopulations, distinguished by differential expression of Ter119 and CD71, are significantly decreased in spleen relative to wild-type controls

• FACS forward scatter (indicator of cell size) is increased in splenic erythroid cells, indicating decreased erythroblast maturation

• however, erythroid cell numbers in the bone marrow, and splenic numbers of T cells, B cells and macrophages are normal

abnormal erythroblast morphology ( J:261784 )

• FACS forward scatter (indicator of cell size) is increased in splenic erythroid cells, indicating decreased erythroblast maturation