UAS sequences drive expression of Hsap\RUNX1::Hsap\RUNX1T1. Hsap\RUNX1::Hsap\RUNX1T1 is a fusion protein that contains the N-terminus and RD domain of Hsap\RUNX1 and almost the entire coding region of Hsap\RUNX1T1.
The Drosophila eye has been used as an in vivo system to investigate the molecular function of the AML1-ETO chimeric protein (which is associated with acute myelogenous leukemia in humans). The AML1-ETO chimeric protein appears to act as a constitutive transcriptional repressor in this system.
Expression of Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa in the larval blood cells under the control of Scer\GAL4lz-gal4 causes an expansion of this hematopoietic lineage and blocks its differentiation into crystal cells.
Expression of Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4lz-gal4 has leukemogenic activity in third instar larvae.
Expression of Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4srp.D.cCa does not affect plasmatocyte development in the embryo, but inhibits crystal cell differentiation.
Expression of Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4lz-gal4 prevents crystal cell differentiation in the embryo and larval lymph gland.
The number of circulating plasmatocytes in larvae expressing Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4lz-gal4 is similar to that of control larvae. The circulating blood cells in the mutant larvae contain 19% differentiated crystal cells and 81% crystal cell progenitors, in contrast to wild type larvae (87% and 13% respectively). Differentiation of crystal cells can be partially restored in larvae expressing Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4lz-gal4 if Scer\GAL80ts.αTub84B is used to inhibit expression at the early third instar larval stage.
Flies expressing Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4lz-gal4 that survive to late pupal stages have glazed eyes in which individual ommatidia cannot be observed. In these flies, part of the eye is frequently covered by scar tissue. In flies that express Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4GMR.PF, eyes are greatly reduced in size and no ommatidia are visible. There is no evidence of a cone cell-to-photoreceptor transformation in eye discs that express Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4GMR.PF. There is a small reduction in the number of cone cells in larval and pupal eyes expressing Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4lz-gal4.
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4lz-gal4 has lethal - all die before end of pupal stage phenotype, suppressible by pontNIG.4003R, Scer\GAL4lz-gal4
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4lz-gal4 has lethal - all die before end of pupal stage phenotype, suppressible by pontKK101103, Scer\GAL4lz-gal4
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4lz-gal4 has hyperplasia | third instar larval stage phenotype, suppressible by MlfΔ5-3
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4lz-gal4 has lethal | pupal stage phenotype, suppressible by CalpBNIG.cUa, Scer\GAL4lz-gal4
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4GMR.PF has eye phenotype, enhanceable by BroUAS.cLa, Scer\GAL4GMR.PF
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4GMR.PF has eye phenotype, enhanceable by BgbUAS.cLa, Scer\GAL4GMR.PF
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4lz-gal4 has embryonic/larval crystal cell | larval stage phenotype, suppressible by pontKK101103, Scer\GAL4lz-gal4
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4lz-gal4 has embryonic/larval hemocyte | increased number | larval stage phenotype, suppressible by pontNIG.4003R, Scer\GAL4lz-gal4
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4lz-gal4 has embryonic/larval crystal cell | larval stage phenotype, suppressible by pontNIG.4003R, Scer\GAL4lz-gal4
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4lz-gal4 has embryonic/larval hemocyte | increased number | larval stage phenotype, suppressible by pontKK101103, Scer\GAL4lz-gal4
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4lz-gal4 has embryonic/larval crystal cell phenotype, suppressible by CalpBNIG.cUa, Scer\GAL4lz-gal4
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4lz-gal4 has embryonic/larval crystal cell phenotype, suppressible by Df(3L)CalpB-/Df(3L)CalpB-
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4lz-gal4 has embryonic/larval crystal cell phenotype, suppressible by lzUAS.cBa, Scer\GAL4lz-gal4
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4GMR.PF has eye phenotype, suppressible | partially by +/Df(3L)Bgb-K4
Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa, Scer\GAL4GMR.PF has eye phenotype, suppressible by lzUAS.cBa, Scer\GAL4GMR.PF
Expression of pontNIG.4003R suppresses the lethality seen when Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa is expressed under the control of Scer\GAL4lz-gal4. The increase in lz positive larval hematopoietic cells is suppressed and differentiation into crystal cells is partially restored.
Expression of pontKK101103 suppresses the lethality seen when Hsap\RUNX1::Hsap\RUNX1T1UAS.cMa is expressed under the control of Scer\GAL4lz-gal4. The increase in lz positive larval hematopoietic cells is suppressed and differentiation into crystal cells is partially restored.
The leukemogenic phenotype of Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa-expression via Scer\GAL4lz-gal4 is almost abolished in MlfΔ5-3 mutant larvae.
Differentiation of crystal cells is restored in larvae expressing Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4lz-gal4 if they are also co-expressing CalpBNIG.cUa.
Differentiation of crystal cells is significantly restored in larvae expressing Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4lz-gal4 if they are also co-expressing lzScer\UAS.cBa.
Differentiation of crystal cells is restored in larvae expressing Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa under the control of Scer\GAL4lz-gal4 in a Df(3L)CalpB-/Df(3L)CalpB- background.
Coexpression of BroScer\UAS.cLa or BgbScer\UAS.cLa increases the severity of the Scer\GAL4GMR.PF>Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa phenotype at 22oC leading to eyes that are greatly reduced in size.
In flies heterozygous for Df(3L)Bgb-K4, the Scer\GAL4GMR.PF>Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa phenotype is partially suppressed.
Coexpression of lzScer\UAS.cBa suppresses the Scer\GAL4GMR.PF>Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa eye phenotype.
Expressing BroScer\UAS.cLa or BgbScer\UAS.cLa increases the severity of the Scer\GAL4GMR.PF>Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa phenotype at 22oC leading to eyes that are greatly reduced in size. In flies that carry one copy of the Df(3L)Bgb-K4 mutation, the Scer\GAL4GMR.PF>Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa phenotype is partially suppressed. Coexpression of lzScer\UAS.cBa suppresses the Scer\GAL4GMR.PF>Hsap\RUNX1::Hsap\RUNX1T1Scer\UAS.cMa eye phenotype
B. Mathey-Prevot