Phenotypes associated with this allele

• Allele Symbol: Runx1^tm1Medv
• Allele Name: targeted mutation 1, Alexander Medvinsky
• Allele ID: MGI:3625885
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Runx1^tm1Medv/Runx1^tm1Medv	involves: 129P2/OlaHsd	MGI:3626258
cn2	Runx1^tm2.1(cre/Esr1*)Ims/Runx1^tm1Medv	involves: 129P2/OlaHsd * C57BL/6	MGI:5316037
cn3	Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor^+ Runx1^tm2.1(cre/Esr1*)Ims/Runx1^tm1Medv	B6.Cg-Gt(ROSA)26Sor^tm1(EYFP)Cos Runx1^tm2.1(cre/Esr1*)Ims	MGI:5316038
cn4	Pdgfra^tm1.1(cre/Esr1*)Nshk/Pdgfra^+ Runx1^tm1Medv/Runx1^tm1Medv	involves: 129P2/OlaHsd * C57BL/6NCrlj * CBA/JNCrlj	MGI:5490465

Genotype
MGI:3626258

hm1

• Allelic Composition: Runx1^tm1Medv/Runx1^tm1Medv
• Genetic Background: involves: 129P2/OlaHsd

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:106769 )

• begin to die around E11.5 with all dead by E13

hematopoietic system

anemia ( J:106769 )

• severe anemia with very few red cells in the fetal liver

impaired hematopoiesis ( J:106769 )

• at E9.5 to E11.5, cells isolated from the fetal liver and yolk sac fail to produce hematopoietic colonies

cardiovascular system

hemorrhage ( J:106769 )

• seen in the central nervous system by E11.5

Genotype
MGI:5316037

cn2

• Allelic Composition: Runx1^{tm2.1(cre/Esr1*)Ims}/Runx1^tm1Medv
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

neonatal lethality ( J:182232 )

• maternal injection of 200-250 mg of 4-hydroxytamoxifen (4-OHT) on E6.5 or E7.5 rescues prenatal lethality, but pups, although born apparently normal, are unable to feed and die within 1 day of birth

embryonic lethality during organogenesis, complete penetrance ( J:182232 )

• all embryos die around E12.5

• maternal injection of 5-6 mg of 4-hydroxytamoxifen (4-OHT) on E6.5 or E7.5 to reactivate the Runx1^lacZ allele rescues 90-100% of the E12.5 lethality; similarly, a low dose of tamoxifen (2 mg) at E7.5 also results in robust (80-100%) rescue of lethality assayed at E16.5 or P0

• reactivation of the Runx1^lacZ allele with maternal tamoxifen treatment at E8.0, 8.5, 9.0, or 9.5 does not rescue the hemorrhagic or liver anemia phenotypes; pregastrulation tamoxifen injection at E5.5 does not result in embryo rescue

hematopoietic system

hematopoietic system phenotype ( J:182232 )

N • with maternal injection of high-dose tamoxifen on E7.5 to induce Runx1 reactivation, restoration of definitive hematopoiesis is observed by E16.5; FACS analyses of blood cell populations are similar to control heterozygous cells

abnormal hematopoietic system morphology/development ( J:182232 )

• tamoxifen treatment at times after E7.5 results in no rescue of definitive hematopoietic progenitor cells; only a few progenitors can be observed with tamoxifen treatment at E8.5 with none found with later treatment timepoints

anemia ( J:182232 )

• embryos exhibit severe liver anemia

cardiovascular system

hemorrhage ( J:182232 )

• embryos display a severe hemorrhagic phenotype

Genotype
MGI:5316038

cn3

• Allelic Composition: Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺; Runx1^{tm2.1(cre/Esr1*)Ims}/Runx1^tm1Medv
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^tm1(EYFP)Cos Runx1^{tm2.1(cre/Esr1*)Ims}

hematopoietic system

hematopoietic system phenotype ( J:182232 )

N • with maternal injection of high-dose tamoxifen on E7.5 to induce Runx1 reactivation, trasnsplanted, hematopoietic stem cells were isolated and injected into irradiated recipients for a long-term competitive repopulation assay; at E14.5 and E16.5, no signficant differences in reconstitution levels of hematopoietic cells is observed relative to controls

N • secondary transplantation of yolk sac-derived bone marrow cells from the primary recipients 12 months following primary transplantation resulted in long-term engraftment

abnormal hematopoietic system morphology/development ( J:182232 )

• exposure of embryos to tamoxifen at E10.5 fails to result in observation of CD45+ definitive hematopoietic cells in the aorta-gonad-mesonephros (AGM) region (no rescue of definitive hematopoiesis), whereas after exposure to tamoxifen at E7.5, a large population of CD45-positive cells are detected

Genotype
MGI:5490465

cn4

• Allelic Composition: Pdgfra^{tm1.1(cre/Esr1*)Nshk}/Pdgfra⁺; Runx1^tm1Medv/Runx1^tm1Medv
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6NCrlj * CBA/JNCrlj

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:193389 )

• rescued embryos (tamoxifen treatment at E7.5) do not survive beyond E12.5

hematopoietic system

anemia ( J:193389 )

• rescued embryos (tamoxifen treatment at E7.5) are modestly anemic

abnormal hematopoietic cell number ( J:193389 )

• with tamoxifen treatment at E7.5, Runx1 expression is restored in the Pdgfra+ve mesoderm and this partially restores CD45+ve and Lin-Kit-Sca1+ve (KSL) hematopoietic cells (HPCs) in the fetal liver at E12.5; these populations are absent without tamoxifen treatment

• with tamoxifen treatment at E7.5, partial recovery of colony forming units (CFUs) from liver cells grown on methycellulose is observed, but without tamoxifen, fetal liver cells fail to generate colonies

integument

pallor ( J:193389 )

• rescued embryos (tamoxifen treatment at E7.5) are pale