Imprecise excision of the P{SUPor-P}CG14879KG03250 insertion, resulting in a deletion that removes 278bp of the Manf open reading frame, including the first 2 exons and part of the third exon.
neurite & dopaminergic neuron | larval stage
ManfΔ96/+ heterozygous adult flies show decreased eye tissue regeneration capacity upon UV radiation induced damage (inflicted during pupal stage) compared to wild-type.
ManfΔ96 homozygous clones are able to survive and differentiate into glia and dopaminergic neurons, similar to surrounding control cells.
Mutant larvae show a significant increase in dopamine levels in total larval lysates compared to wild type.
Homozygotes die as later first instar larvae or immediately after the delayed first moult with defects in behaviour; the larvae atypically wander away from the food, then move more slowly and finally freeze, immobilised but still responding to touch.
Embryonic neural development occurs normally in homozygotes.
The volume of DA neurites is significantly diminished in homozygous larvae, whereas the neuronal somae persist. The neuritic degeneration occurs mostly in the abdominal area of the ventral nerve cord. There is no significant change in the neurite volume of serotonergic neurons or in the volume of the motorneuron subpopulation in these larvae.
ManfΔ96 embryos lacking both maternal and zygotic Manf[+] function develop normally until late stage 16, but show severe defects thereafter; the ventral nerve cord (VNC) becomes overcondensed compared to wild type. At early stage 16, the neuropile of the VNC still resembles that of wild type, but by late stage 17, degradation of axonal membranes is seen, starting at the border of the glia and neuropile. In addition, cell body glial cells appear highly electron dense and contain remnants of cell debris. In the VNC, dying cells with poor and bleached cytoplasm, swollen nuclei and with dilated endoplasmic reticulum and other organelles are seen, which is atypical for conventional apoptosis. The cuticle of these embryos is defective; all cuticular layers are disorganised.
ManfΔ96 has lethal - all die during first instar larval stage phenotype, suppressible by Scer\GAL4da.G32/Hsap\MANFUAS.WT
ManfΔ96 has lethal - all die during first instar larval stage phenotype, suppressible by Hsap\CDNFUAS.WT/Scer\GAL4da.G32
ManfΔ96 has lethal - all die during first instar larval stage phenotype, suppressible by Scer\GAL469B/Hsap\MANFUAS.WT
ManfΔ96 has lethal - all die during first instar larval stage phenotype, suppressible by Scer\GAL4da.G32/Hsap\MANF::Hsap\CDNFUAS.cLa
ManfΔ96 has lethal - all die during first instar larval stage phenotype, suppressible by Scer\GAL4da.G32/Hsap\MANFΔRTDL.UAS
ManfΔ96 has lethal | recessive | larval stage phenotype, suppressible by Hsap\MANFUAS.9C/Scer\GAL4Tub.PU
ManfΔ96 has lethal | recessive | larval stage phenotype, suppressible by Hsap\MANFUAS.9C/Scer\GAL4da.G32
ManfΔ96 has lethal - all die during first instar larval stage phenotype, non-suppressible by Scer\GAL4da.G32/Hsap\MANFN.UAS
ManfΔ96 has lethal - all die during first instar larval stage phenotype, non-suppressible by Hsap\MANFC.UAS/Scer\GAL4da.G32
ManfΔ96 has lethal - all die during first instar larval stage phenotype, non-suppressible by Scer\GAL4da.G32/Hsap\MANFC.Δss.UAS
ManfΔ96 has lethal - all die during first instar larval stage phenotype, non-suppressible by Scer\GAL4da.G32/Hsap\CDNFN.UAS
ManfΔ96 has lethal - all die during first instar larval stage phenotype, non-suppressible by Hsap\CDNFC.UAS/Scer\GAL4da.G32
ManfΔ96 has lethal - all die during first instar larval stage phenotype, non-suppressible by Hsap\CDNFC.Δss.UAS/Scer\GAL4da.G32
ManfΔ96 has lethal - all die during first instar larval stage phenotype, non-suppressible by Hsap\CDNFUAS.WT/Scer\GAL469B
ManfΔ96 has lethal - all die during first instar larval stage phenotype, non-suppressible by Scer\GAL469B/Hsap\MANF::Hsap\CDNFUAS.cLa
ManfΔ96 has lethal - all die during first instar larval stage phenotype, non-suppressible by Hsap\MANFΔRTDL.UAS/Scer\GAL469B
Scer\GAL4da.G32-mediated expression of Hsap\MANFScer\UAS.WT or Hsap\CDNFScer\UAS.WT efficiently rescues ManfΔ96 mutant lethality to adulthood.
Scer\GAL4da.G32-mediated expression of Hsap\MANFN.Scer\UAS, Hsap\MANFC.Scer\UAS or Hsap\MANFC.Δss.Scer\UAS does not rescue ManfΔ96 larval lethality.
Scer\GAL4da.G32-mediated expression of Hsap\CDNFN.Scer\UAS, Hsap\CDNFC.Scer\UAS or Hsap\CDNFC.Δss.Scer\UAS does not rescue ManfΔ96 larval lethality.
Scer\GAL469B-mediated expression of Hsap\MANFScer\UAS.WT but not Hsap\CDNFScer\UAS.WT rescues ManfΔ96 mutant lethality to adulthood.
Scer\GAL4da.G32-mediated, but not Scer\GAL469B-mediated, expression of Hsap\MANF::Hsap\CDNFScer\UAS rescues ManfΔ96 mutant lethality to adulthood.
Scer\GAL4da.G32-mediated, but not Scer\GAL469B-mediated, expression of Hsap\MANFΔRTDL.Scer\UAS rescues ManfΔ96 mutant lethality to adulthood.
Expression of Hsap\MANFScer\UAS.cPa under the control of one of Scer\GAL4da.G32 or Scer\GAL4tub significantly rescues the larval lethality of ManfΔ96 animals (assayed by survival into the pupal stage).
Manf[+]/ManfΔ96 is rescued by Scer\GAL4Hml.Δ/ManfUAS.cPa
ManfΔ96 is rescued by Scer\GAL4da.G32/ManfUAS.cPa
ManfΔ96 is rescued by ManfUAS.cPa/Scer\GAL469B
ManfΔ96 is rescued by Scer\GAL4da.G32/ManfΔRSEL.UAS
ManfΔ96 is rescued by ManfNMG1.UAS/Scer\GAL4da.G32
ManfΔ96 is rescued by ManfNMG2.UAS/Scer\GAL4da.G32
ManfΔ96 is rescued by ManfNMG2.UAS/Scer\GAL469B
ManfΔ96 is rescued by Scer\GAL4da.G32/ManfUAS.cPa
ManfΔ96 is rescued by Scer\GAL4Tub.PU/ManfUAS.cPa
ManfΔ96 is rescued by ManfUAS.cPa/Scer\GAL469B
ManfΔ96 is partially rescued by ManfΔRSEL.UAS/Scer\GAL469B
ManfΔ96 is not rescued by Scer\GAL4da.G32/ManfN.UAS
ManfΔ96 is not rescued by ManfC.UAS/Scer\GAL4da.G32/ManfN.UAS
ManfΔ96 is not rescued by Scer\GAL4da.G32/ManfN.UAS/ManfC.Δss.UAS
ManfΔ96 is not rescued by Scer\GAL4da.G32/ManfN.Δss.UAS
ManfΔ96 is not rescued by ManfC.UAS/Scer\GAL4da.G32/ManfN.Δss.UAS
ManfΔ96 is not rescued by Scer\GAL4da.G32/ManfN.Δss.UAS/ManfC.Δss.UAS
ManfΔ96 is not rescued by ManfC.UAS/Scer\GAL4da.G32
ManfΔ96 is not rescued by Scer\GAL4da.G32/ManfC.Δss.UAS
ManfΔ96 is not rescued by ManfΔss.UAS/Scer\GAL4da.G32
ManfΔ96 is not rescued by Scer\GAL4da.G32/ManfC129S.UAS
ManfΔ96 is not rescued by ManfNMG1.UAS/Scer\GAL469B
ManfΔ96 is not rescued by ManfUAS.cPa/Scer\GAL4path-c135
The increased severity of eye degeneration after exposure of one eye to UV irradiation during pupal stage characteristic for ManfΔ96/+ adults can be rescued by expression of ManfScer\UAS.cPa under the control of Scer\GAL4Hml.Δ.
ManfScer\UAS.cPa expression driven by Scer\GAL4da.G32 rescues the early larval lethality of ManfΔ96 mutants and normalizes ManfΔ96 larval dopamine to wild type levels.
Expression of ManfN.Scer\UAS, ManfN.Δss.Scer\UAS, ManfC.Scer\UAS, or ManfC.Δss.Scer\UAS driven by Scer\GAL4da.G32 does not rescue the early larval lethality of ManfΔ96 mutants.
ManfN.Scer\UAS and ManfC.Scer\UAS co-expression driven by Scer\GAL4da.G32 does not rescue the early larval lethality of ManfΔ96 mutants.
ManfN.Scer\UAS and ManfC.Δss.Scer\UAS co-expression driven by Scer\GAL4da.G32 does not rescue the early larval lethality of ManfΔ96 mutants.
ManfN.Δss.Scer\UAS and ManfC.Scer\UAS co-expression driven by Scer\GAL4da.G32 does not rescue the early larval lethality of ManfΔ96 mutants.
ManfN.Δss.Scer\UAS and ManfC.Δss.Scer\UAS co-expression driven by Scer\GAL4da.G32 does not rescue the early larval lethality of ManfΔ96 mutants.
ManfΔss.Scer\UAS expression driven by Scer\GAL4da.G32 does not rescue the early larval lethality of ManfΔ96 mutants. Increasing the copy number of the driver and/or responder transgene makes no difference.
ManfΔRSEL.Scer\UAS expression driven by Scer\GAL4da.G32 rescues the early larval lethality of ManfΔ96 mutants to adulthood, and normalizes ManfΔ96 larval dopamine to wild type levels.
ManfC129S.Scer\UAS expression driven by Scer\GAL4da.G32 does not rescue the early larval lethality of ManfΔ96 mutants, though one of three insertions did result in very few rescued pupae.
ManfNMG1.Scer\UAS expression driven by Scer\GAL4da.G32 rescues the early larval lethality of ManfΔ96 mutants, and normalizes ManfΔ96 larval dopamine to wild type levels.
ManfNMG2.Scer\UAS expression driven by Scer\GAL4da.G32 rescues the early larval lethality of ManfΔ96 mutants, and normalizes ManfΔ96 larval dopamine to wild type levels.
ManfScer\UAS.cPa expression driven by Scer\GAL469B rescues the early larval lethality of ManfΔ96 mutants.
ManfNMG2.Scer\UAS expression driven by Scer\GAL469B rescues the early larval lethality of ManfΔ96 mutants.
ManfΔRSEL.Scer\UAS expression driven by Scer\GAL469B only partially rescues the early larval lethality of ManfΔ96 mutants.
ManfNMG1.Scer\UAS expression driven by Scer\GAL469B does not rescue the early larval lethality of ManfΔ96 mutants.