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General Information
D. melanogaster
FlyBase ID
Feature type
Associated gene
Associated Insertion(s)
Carried in Construct
Key Links
    Nature of the Allele
    Mutations Mapped to the Genome
    Additional Notes
    Nucleotide change:


    Reported nucleotide change:


    Amino acid change:

    G181D | Dif-PA; G181D | Dif-PB; G181D | Dif-PC; G181D | Dif-PD

    Reported amino acid change:


    Associated Sequence Data
    DNA sequence
    Protein sequence
    Progenitor genotype
    Nature of the lesion

    Amino acid replacement: G181D.

    Nucleotide substitution: G1104A.

    Expression Data
    Reporter Expression
    Additional Information
    Marker for
    Reflects expression of
    Reporter construct used in assay
    Human Disease Associations
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 1 )
    Modifiers Based on Experimental Evidence ( 0 )
    Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
    Disease-implicated variant(s)
    Phenotypic Data
    Phenotypic Class
    Phenotype Manifest In
    Detailed Description

    Dif1/Df(2L)Exel7068 flies have survival rates similar to wild type in response to Sindbis virus infection.

    Dif1/Dif1 mutants do not exhibit any significant difference in survival rate of flies either untreated or treated with Leishmania amastigotes, as compared to wild type.

    VA1d olfactory receptor neuron axon targeting is normal in mutant flies.

    RelE20 mutant flies exposed to non-replicating P. aeruginosa bacteria display a mild immunity and slightly extended survival rates compared to non-exposed Dif1 flies. However, this reaction is not as great as in wild-type flies.

    Dif1/Dif2 flies that have been challenged with vesicular stomatitis virus show levels of viral replication that are not significantly different to that seen in wild-type controls.

    Mutant flies are highly susceptible to infection with L. monocytogenes (via septic injury) or to infection with B. bassiana.

    Mutant flies show reduced survival compared to wild-type controls after natural infection with B. bassiana.

    Dif1 flies infected at 2-4 days of age exhibit a shorter survival time than control flies, regardless of sex. Approximately 15% of Dif1 flies die in the first two days of life, regardless of infection. Control flies live long than Dif1 flies, with fungal infection slightly decreasing longevity in both sets of flies, regardless of sex.

    In controlled conditions, where flies are virgin, and larvae aren't crowded, Dif1 flies outlive control flies, and females outlive males.

    Dif1 flies do not exhibit a difference to controlled flies in terms of resistance to heat.

    Dif1 mutant flies survive for a shorter time after fungal infection, compared to controls, with males tending to survive slightly longer than females, while no sex difference is seen in controls.

    Mutant flies that are infected with E. coli one day prior to infection with either X. nematophila or P. luminescens show the same phenotype as wild-type flies (increased survival after infection with either X. nematophila or P. luminescens due to partial protection by the prior infection with E. coli).

    Dif1 mutant flies show similar levels of viral replication and viral titers 5 days after intrathoracic infection with 200 pfu of Sindbis virus as controls.

    Short term starvation does not improve the survival of Dif1 mutant flies following infection with Gram-positive bacteria.

    Dif1 flies show a normal lifespan on dead yeast medium and on live yeast medium. Dif1 flies have a low number of living yeast in the gut (assayed as the number of colony-forming units from homogenates of surface-sterilized intestines), as do wild-type flies.

    Homozygous flies show ectopic macrochaetae in 29% of heminota analysed at 18[o]C (this phenotype is not seen at 25[o]C). In most cases, one ectopic macrochaeta is seen per heminotum.

    Heterozygous flies show ectopic dorsocentral bristles in the medial notum in 8% of heminota at 18[o]C.

    Dif1/Df(2L)J4 and Dif1/Dif2 larvae do not show R2-R5 photoreceptor axon targeting defects in the developing visual system.

    Dif1 flies show similar mortality levels to wild-type flies in response to feeding with both the ROS-resistant KNU53775 yeast strain and a standard yeast strain (W303).

    The mean circulating hemocyte number of Dif1/Df(2L)TW119 mutants is not statistically different from that of controls.

    Mutant flies show similar survival rates as control flies following natural infection (feeding with contaminated food) with either "Ecc-15" (P.carotovorum.carotovorum), S.cerevisiae or M.luteus.

    Dif1 flies show a normal survival rate after natural infection with "Ecc15" (P.carotovorum.carotovorum).

    Dif1 mutant flies exhibit increased susceptibility to DXV virus infection compared to wild-type. Dif1 flies succomb to anoxia induced death approximately 48 hours earlier than wild-type. Viral titer levels are also found to be approximately 40-times higher than observed in wild-type at 3 days post-infection.

    Dif1 and Dif1/Df(2L)J4b mutant flies infected with P.acidolactici, E.faecalis, or S.saprophyticus die more rapidly than wild-type controls.

    Flies hemizygous for Dif1/Df(2L)J4b exhibit an extreme reduction in the inducibility of Drs 48hrs after immune challenge. In contrast, Dif1/Df(2L)J4b flies carrying DifαTub84B.PM express Drs at almost wild-type levels under similar conditions.

    Dif1 mutant flies are significantly more sensitive to fungal infection than wild-type flies. Two and a half days after infection with the entomopathogenic fungus B. bassiana, most Dif1 mutants have died, whereas ~90% of the wild-type flies are still alive. The survival curves are similar for homozygous and hemizygous Dif1/Df(2L)TW119 flies.

    Dif1 mutants display a resistance to bacterial infections (whether gram-positive, gram-negative, or mixtures), similar to that of wild-type flies.

    Mutant flies show lower resistance to B.bassiana (when their cuticles are coated with spores) than wild-type flies, succumbing rapidly to infection.

    External Data
    Show genetic interaction network for Enhancers & Suppressors
    Phenotypic Class
    Enhanced by
    NOT Enhanced by

    Dif1 has abnormal immune response phenotype, non-enhanceable by key1

    Suppressed by
    NOT suppressed by

    Dif1 has abnormal immune response phenotype, non-suppressible by key1

    NOT Enhancer of

    Dif1 is a non-enhancer of short lived phenotype of tefuatm-8

    Suppressor of
    NOT Suppressor of
    Phenotype Manifest In
    Enhanced by
    Suppressed by
    Suppressor of
    NOT Suppressor of
    Additional Comments
    Genetic Interactions

    Presence of Dif1/Dif1 does not suppress the shorter lifespan in Diedel1/Diedel1 flies after Sindbis virus infection.

    Lamellocyte counts are significantly lower in krzc01503 Dif1 larvae compared to krzc01503 larvae.

    Dif1 fails to suppress the melanotic mass phenotype seen in Atg61 mutant third instar larvae.

    A Dif1 RelE20 double mutant background fails to suppress the melanotic mass phenotype seen in Atg61 mutant third instar larvae.

    A Dif1/Df(2L)J4 RelE20 mutant background fails to suppress the melanotic mass phenotype seen in Atg61 mutant third instar larvae.

    Short term starvation does not improve the survival of Dif1-key1 double mutants following infection with Gram-negative bacteria.

    RelE20 Dif1 double mutant larvae are smaller than wild-type, and about half of the double homozygotes die before reaching adult stages.

    Dif1 dl1 double mutants are small and sluggish and only 3.4% survive to adult. Unchallenged Dif1 dl1 double mutant larvae contain many bacteria and yeast in their haemolymph (as many as 105 microbes per animal), while no microbes are observed in wild-type haemolymph. In microbe-free conditions, in the presence of antibiotics, approximately 33% of Dif1 dl1 double mutants survive to adult stages, thats a 10-fold increase compared to normal conditions. Dif1 dl1 double mutants are able to mount a humoral immune response, but this does not prevent constitutive infection of these animals.

    Dif1 dl1/+ + double heterozygotes exhibit approximately 5000 blood cells per υl of haemolymph, the same as in wild-type flies. In contrast, Dif1 dl1 double homozygotes exhibit a greatly reduced number of haemocytes, approximately 500 per υl - 10-fold fewer than in wild-type. Approximately 15% of Dif1 dl1 haemocytes undergo apoptosis, compared with only 2.3% in wild-type.

    The few blood cells present in Dif1 dl1 mutants exhibit an abnormal morphology. In contrast to wild-type haemocytes, Dif1 dl1 blood cells are enlarged, containing intact intracellular bacteria that are not localised to vacuoles and have not been digested. When Dif1 dl1 larvae are grown on minimal medium in the presence of antibiotics, the number of haemocytes increases 3-fold, to approximately 1400 cells per υl, and the haemocytes are of normal morphology.

    Ubiquitous expression of DifScer\UAS.cIa, driven by Scer\GAL4hs.PB at 25oC (without heat shock) fully rescues the lethality of Dif1 dl1 double mutants.

    Ubiquitous expression of dlScer\UAS.cMa, driven by Scer\GAL4hs.PB at 25oC (without heat shock) fully rescues the lethality of Dif1 dl1 double mutants.

    Expression of dlScer\UAS.cMa in circulating haemocytes, lymph glands, and epidermis, but not in the fat body, under the control of Scer\GAL4e33C, restores normal haemocyte numbers in Dif1 dl1 double mutants. The rescued blood cells are indistinguishable in morphology from wild-type uninfected haemocytes. In addition, the rescued animals have do not have any microbes in their haemolymph and 66% survive to adult stages.

    Expression of dlScer\UAS.cMa in circulating haemocytes, but not in other immune-responsive tissues, under the control of Scer\GAL4He.PZ, results in an absence of microbes from the haemolymph, with approximately 45% of dlScer\UAS.cMa expressing Dif1 dl1 double mutants surviving till adulthood.

    Expression of dlScer\UAS.cMa in circulating haemocytes and lymph gland cells, under the control of Scer\GAL4srp.Hemo, increases blood cell number to approximately 90% of wild-type in Dif1 dl1 double mutants and enables approximately 50% survival till adulthood. The majority of these larvae have no microbes in their haemolymph.

    The melanotic tumour penetrance and circulating hemocyte levels are partially reduced in lwr4-3 Df(2L)TW119/lwr5 Dif1 double mutants, compared to lwr4-3/lwr5 single mutants. However, the amount of lamellocytes is not reduced.

    Dif1 key1 double mutants die at the same rate as Dif1 single mutants when infected with either P.acidolactici, E.faecalis, or S.saprophyticus.

    Dif1 key1 double mutants die at the same rate as Dif1 mutants when their cuticles are coated with spores of B.bassiana.

    Xenogenetic Interactions

    Expression of BacA\p35GMR.PH in the haemocytes, under the control of Scer\GAL4He.PZ in Dif1 dl1 animals results in the number of blood cells per υl of haemolymph increasing 4-fold, to approximately 2200 cells per υl, whereas the blood cell number remains constant in Dif1 dl1 heterozygotes.

    Complementation and Rescue Data
    Images (0)
    Stocks (1)
    Notes on Origin
    External Crossreferences and Linkouts ( 0 )
    Synonyms and Secondary IDs (1)
    References (42)