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General Information
Symbol
Dmel\hopTum
Species
D. melanogaster
Name
FlyBase ID
FBal0005547
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
hopTum-l, hopTum-1, hopTuml, HopTum1, Tum-l
Key Links
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Nucleotide change:

G11366441A

Reported nucleotide change:

G1641A

Amino acid change:

G341E | hop-PA

Reported amino acid change:

G341E

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

Amino acid replacement: G341E.

Mutant protein contains a glycine to glutamic acid substitution.

Amino acid replacement: G341E. Nucleotide substitution: G1641A.

Expression Data
Reporter Expression
Additional Information
Statement
Reference
 
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 ( 1 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In

hindgut & nucleus

Detailed Description
Statement
Reference

hopTum heterozygous adults exhibit a range of small to large tumor frequencies.

Heterozygous adult females contain melanotic tumours. The incidence of lamellocytes as a percentage of the total hemocytes is increased compared to wild type in hemolymph preparations from third instar heterozygous larvae.

Mutant adults contain multiple, large melanotic tumours.

Mutant third instar larvae show an increase in the number of circulating hemocytes compared to controls.

The number of hemocytes is increased in hopTum mutant third instar larvae compared to wild type.

hopTum lymph glands display considerable numbers of lamellocytes when larvae are raised at 23, 25, or 27[o]C.

Lymph glands of hopTum/Y larvae at 72 hours of development show hyperplasia and extensive lamellocyte differentiation. Lamellocytes reproducibly appear in the mutant lymph glands at around 54-56 hours of development at 25[o]C. A large population of lamellocytes are seen in the mutant hemolymph at 72 hours of development, and lamellocytes are reproducibly seen in the mutant hemolymph before 56 hours of development at 25[o]C.

Heterozygous larvae show a massive overproduction of both lamellocytes and non-lamellocyte hemocytes in the hemolymph.

Mutant larvae have a large number of lamellocytes within the circulating hemolymph.

75% of mutant larvae are melanised.

Lymph glands from hopTum/Y animals are hypertrophic and produce increased numbers of hemocytes and lamellocytes.

Heterozygous third instar larvae have melanotic nodules found in the hemocoel or in association with He-positive lymph glands. The melanotic nodules are surrounded by lamellocytes.

Mutant larvae show overproliferation of plasmatocytes in the primary lymph gland lobes and hemocytes aberrantly differentiate into lamellocytes in the secondary lymph gland lobes.

Heterozygotes often have melanotic tumours.

hopTum is dominant semi-lethal at 29oC (survival of females to adulthood is 48% of wild-type).

The proportion of completely melanised tumours by larva is significantly decreased in hopTum larvae parasitised by the G431 L.boulardi strain compared to unparasitised hopTum larvae, while the proportion of partially melanised tumours is significantly increased.

hopTum embryos have nearly twice as many pole cells as wild-type embryos. At stage 3, the pole cells in hopTum mutants change shape and migrate away from the posterior pole, while pole cells in wild-type embryos remain a spherical shape and are confined to the posterior area. Pole cells in the mutants are frequently observed to prematurely transit through the gut and migrate errantly. Such pole cells survive, in contrast to wild-type embryos where errant pole cells are destroyed by apoptosis, and aggregate in ectopic locations. Pole cells from cellularization stage hopTum embryos are more active both in dispersion and translocation movements when observed in Schneider culture medium, than pole cells from wild-type embryos.

In mutants the tracheal pits are larger than in wild-type. The hindgut is also longer than seen in wild-type. The hindgut nuclei in mutants form a single layer and are further apart from each other, giving the appearance of being stretched. The peripheral nervous system of mutants differentiate and grow axons prematurely - the PNS is nearly fully differentiated at stage 12 (as compared to 15 in wild-type).

About a quarter of heterozygous mutant larvae exhibit melanotic tumours when grown at 25oC about half exhibit tumours when grown at 28oC.

Mutant larvae raised at the non-permissive temperature (29oC) have melanotic tumours.

At 28oC, hopTum larvae show a six-fold increase in the concentration of circulating blood cells compared to wild-type larvae. 48% of the plasmatocytes are differentiated into lamellocytes in hopTum larvae compared to 6% in wild-type larvae. The larvae have overgrown and melanised lymph glands.

The concentration of circulating hemocytes in hemizygous larvae is increased compared to controls. The distribution of blood cell types is altered compared to wild type; in the mutant larvae 63.2% are plasmatocytes (more than 99% in controls), 11.4% are podocytes (less than 0.1% in controls) and 25.4% are lamellocytes (0.1% in controls).

100% of hemizygous third instar larvae show multiple melanotic capsules at 18oC, 25oC and 29oC. Hemizygous adults show multiple melanotic capsules at 25oC.

At 25oC 37% of heterozygous mutant adult females have at least one abdominal tumour.

When raised at 25oC, second instar mutant larvae have abundant (10-15%) lamellocytes in circulation and in some larvae lamellocytes can be seen in lymph gland lobes. Melanotic tumours are not yet present. Lamellocyte numbers increase very rapidly in the course of the third instar stage and but the end of the instar represent close to 50% of the circulating blood cell population. Plasmatocytes frequently show abnormal oversized features. Lamellocytes are very abundant in the lymph glands before pupariation. Crystal cells are rarely round in mutant larvae.

Larvae contain free-floating melanotic masses.

Heterozygotes grown above 25oC have reduced viability and develop melanotic tumors.

At high culture temperatures, abnormalities in hemocyte proliferation and differentiation, melanization of hematopoetic and gut tissue and recessive lethality result.

Formation of melanotic tumours and hypertrophy of the lymph glands. Tissue transplantation indicates the lymph glands can autonomously generate melanotic masses associated with the mutation.

Homozygotes raised at 29oC form black melanotic masses, haematopoietic defects. Lymph gland material transplanted into a wild type host that is cultured at 29oC causes the appearance of melanotic masses in the abdominal cavity and/or in the leg joints, bloating is also observed. Elevated levels of lamellocytes are found in the haemolymph due to overproliferation and premature differentiation.

Blood cell neoplastic phenotype.

Hematopoietic neoplasms, overproliferation of hemocyte stem cells in the larval lymph gland and premature differentiation of circulating haemocytes. Lethality occurs at 29oC.

Dominant tumorous gene that is a temperature-sensitive lethal at 29oC in hemizygous males and homozygous females; about two-thirds of the hemizygous males survive at 18oC and one-quarter of these have melanotic tumors. Males raised at 26oC and heterozygous females raised at 29oC survive to adulthood, but show melanotic masses in the abdominal cavity or small black specks in the legs, wings, or thorax. Mutant larvae kept at 29oC show enlargement of the lymph glands in the late second- or early third instar larvae, but no melanotic masses. By mid third instar, the lymph glands are large and diffuse and the gastric caeca have become encapsulated and melanized. By late third instar, the larvae have melanotic masses in the body cavity, lack lymph glands and have reduced, encapsulated and melanized gastric caeca as well as encapsulated and melanized muscles and fat bodies. These mutants do not survive beyond the late third instar or the early pupal stage. When lymph glands from Tum larvae are injected into adult female hosts, transplantable neoplasms are produced. Melanization, at first associated with the leg joints and later with the head, thorax and abdomen, takes place; also abdominal bloating. The lymph glands become melanotic and the abdomen is filled with encapsulated masses before the premature death of the injected individuals. Injection of Tum tissue other than lymph glands fails to produce these effects. The melanotic neoplasms can be transplanted into a succession of hosts in which they produce the same abnormalities. The neoplastic cells resemble hemocytes; some cell lines are melanotic and others are unpigmented, but in both types, the tissue, when transplanted, grows rapidly in the hosts and kills them.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
NOT Enhanced by
Statement
Reference
Suppressed by
Statement
Reference

hopTum has melanotic mass phenotype | dominant phenotype, suppressible | partially by Stat92E[+]/Stat92E06346

hopTum has partially lethal - majority die | dominant | heat sensitive phenotype, suppressible | partially by CycE[+]/CycE05206

hopTum has partially lethal - majority die | dominant | heat sensitive phenotype, suppressible by Cdk43/Cdk4[+]

hopTum has melanotic mass phenotype phenotype, suppressible by Raf12

hopTum has abnormal immune response | heat sensitive phenotype, suppressible | partially by ecd1

hopTum has melanotic mass phenotype | heat sensitive phenotype, suppressible | partially by ecd1

hopTum has partially lethal phenotype, suppressible by Stat92E06346

hopTum has lethal phenotype, suppressible by awdK

NOT suppressed by
Statement
Reference

hopTum has lethal | heat sensitive phenotype, non-suppressible by Hipk[+]/Hipk4

hopTum has lethal | heat sensitive phenotype, non-suppressible by Scer\GAL4Hml.Δ/HipkKK107857

hopTum has hyperplasia | third instar larval stage phenotype, non-suppressible by Raf12

hopTum has melanotic mass phenotype phenotype, non-suppressible by Dsor1S-1221

hopTum has melanotic mass phenotype phenotype, non-suppressible by Raf11

Suppressor of
Statement
Reference

hopTum/hop[+] is a suppressor | partially of visible | P-stage phenotype of Ipk220B

hopTum/hop[+] is a suppressor | partially of hypoplasia | P-stage phenotype of Ipk220B

hopTum/hop[+] is a suppressor of visible phenotype of Scer\GAL4Tub.PU, cswN308D.UASp

NOT Suppressor of
Statement
Reference
Other
Phenotype Manifest In
Enhanced by
NOT Enhanced by
Suppressed by
Statement
Reference

hopTum has lamellocyte | increased number phenotype, suppressible by kay1/kay[+]

hopTum has melanotic mass phenotype, suppressible | partially by Stat92E[+]/Stat92E06346

hopTum has melanotic mass phenotype, suppressible | partially by BRWD305842/BRWD3[+]

hopTum has hemocyte | increased number phenotype, suppressible by Dsor1S-1221

hopTum has lamellocyte | increased number phenotype, suppressible by Raf12

hopTum has melanotic mass phenotype, suppressible by Raf12

hopTum has hemocyte | increased number phenotype, suppressible by Raf11

hopTum has lamellocyte | increased number phenotype, suppressible by Raf11

hopTum has hemocyte | increased number phenotype, suppressible by Dsor1XS520

hopTum has lamellocyte phenotype, suppressible | partially by Stat92E[+]/Stat92E06346

hopTum has phenotype, suppressible by Stat92E06346

hopTum has melanotic mass phenotype, suppressible by awdK

hopTum has hemocyte phenotype, suppressible by awdK

NOT suppressed by
Statement
Reference

hopTum has melanotic mass phenotype, non-suppressible by Dsor1S-1221

hopTum has hemocyte | increased number phenotype, non-suppressible by Raf12

hopTum has embryonic/larval lymph gland phenotype, non-suppressible by Raf12

hopTum has embryonic/larval lymph gland phenotype, non-suppressible by Raf11

hopTum has melanotic mass phenotype, non-suppressible by Raf11

hopTum has lamellocyte phenotype, non-suppressible by brm[+]/brm2

Suppressor of
Statement
Reference

hopTum/hop[+] is a suppressor | partially of wing | P-stage phenotype of Ipk220B

hopTum/hop[+] is a suppressor of wing vein | ectopic phenotype of Scer\GAL4Tub.PU, cswN308D.UASp

Additional Comments
Genetic Interactions
Statement
Reference

hopTum/+ partially suppresses the small wing phenotype but does not suppress lethality in Ipk220B/Ipk220B pupae.

The penetrance of the melanotic mass phenotype seen in hopTum/+ females is enhanced if they also carry one copy of pzg66 or of E(bx)Nurf301-2.

The incidence of lamellocytes as a percentage of the total hemocytes in hemolymph preparations is increased in hopTum/+ ; pzg66/+ larvae compared to hopTum/+ larvae.

Expression of bazScer\UAS.cKa under the control of Scer\GAL4dome-PG5 reduces the number of circulating hemocytes in hopTum third instar larvae.

One copy of EcRKG04522 is unable to suppress the hemocyte overproliferation seen in hopTum mutant third instar larvae.

One copy of EcRQ50st is unable to suppress the hemocyte overproliferation seen in hopTum mutant third instar larvae.

kay1/+ significantly suppresses the number of lamellocytes in the hemolymph of hopTum/+ larvae.

The frequency of melanisation seen in hopTum larvae is reduced (from 75% to 28% of larvae) when they are also expressing CG42640dsRNA.Scer\UAS under the control of Scer\GAL4da.G32.

Lymph glands in hopTum/Y animals expressing ushScer\UAS.cFa under the control of Scer\GAL4Cg.PA are hypertrophic and produce lamellocytes, although the number of circulating lamellocytes is reduced by 90%.

Removing one copy of Ptp61F, with the Df(3L)ED4238 deficiency, in hopTum heterozygous females leads to a significant decrease in the survival rate and a dramatic enhancement in the formation of melanotic tumors (89.83% of flies with tumors compared to 19.43% of hopTum/+ flies).

Hemocytes in the secondary lymph gland lobes of hopTum MybMH107 double mutant larvae fail to overproliferate and do not adopt the flattened shape characteristic of differentiated lamellocytes.

One copy of BRWD305842 or Stat92E06346 reduces the size and the frequency of the melanotic tumours induced by hopTum/+. Expression of Ptp61Fc.Scer\UAS under the control of Scer\GAL4Cg.PA suppresses the formation of melanotic tumours that is seen in a hopTum/+ background. Expression of Ptp61Fa.Scer\UAS under the control of Scer\GAL4Cg.PA does not suppress the formation of melanotic tumours that is seen in a hopTum/+ background.

Survival to adulthood of hopTum/+ females raised at 29oC is restored to 96% wild-type levels by heterozygosity for Cdk43 and to 85% by heterozygosity for CycE05206.

The addition of Df(3L)3643 or E(bx)Nurf301-2 enhances the melanotic tumour phenotype seen in hopTum/+ larvae, so that over half exhibit tumours at 25oC and 3/4 at 28oC (in the case of Df(3L)3643/+) and over 60% exhibit tumours at 25oC and 80% at 28oC, in the case of E(bx)Nurf301-2.

At 28oC, less than 3% lamellocytes are seen in phl12 hopTum larvae. Plasmatocytes with abnormal morphology are occasionally seen in these animals; some blood cells are larger than the plasmatocytes normally seen in wild-type larvae, while others have processes or an elongated morphology. The overproliferation of blood cells seen in hopTum larvae is not suppressed by phl12. phl12 hopTum larvae have reduced melanotic tumour formation compared to hopTum larvae, but the lymph glands are still overgrown. At 28oC, the increased differentiation of blood cells into lamellocytes and the increased accumulation of blood cells seen in hopTum larvae is completely suppressed by phl11. All hemizygous phl11 hopTum larvae have overgrown and melanised lymph glands, similar to that seen in hopTum mutants cultured at 28oC. Dsor1S-1221 or Dsor1XS520 block differentiation of hopTum blood cells into lamellocytes and the increased accumulation of blood cells seen in hopTum larvae is strongly inhibited in the double mutant larvae. Dsor1S-1221 hopTum mutant lymph glands are overgrown and melanised.

mxcG43 hopTum/Y lymph glands contain differentiated hemocytes. The increased concentration of circulating hemocytes seen in hopTum larvae is significantly reduced by brm2/+, although lamellocyte ratios remain unchanged in the double mutants.

Lowering of ecdysone levels in hopTum/Y; ecd1/ecd1 resulted in mild suppression of the hopTum melanotic capsule phenotype and the encapsulation capacity on parasitisation by L. boulardi G486.

The addition of Su(var)2-1003697 or Df(2R)Np3 enhances the tumor phenotype seen in hopTum flies, over doubling the frequency of flies with at least one tumour. The addition of Su(var)2-10537.Scer\UAS driven by Scer\GAL4hs.PB significantly suppresses the tumourigenic phenotype of hopTum, decreasing the proportion of flies with tumours to about half.

hopTum; domk08108 double mutant larvae contain melanotic masses, although their frequency is markedly reduced compared to hopTum single mutant larvae and the masses are devoid of hemocytes.

Stat92E06346 and Stat92EHJ can suppress the premature differentiation and aggregation but not the overproliferation of larval haemocytes.

Suppresses the ectopic wing vein phenotype of Stat92EHJ.

Lethality of hopTum rescued by awdK alleviating premature formation of circulating haemocytes and melanotic mass formation in temperature- dependent fashion.

Xenogenetic Interactions
Statement
Reference
Complementation and Rescue Data
Comments
Images (0)
Mutant
Wild-type
Stocks (1)
Notes on Origin
Discoverer
Comments
Comments

Encodes an activated form of hop.

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (24)
Reported As
Symbol Synonym
Tum
Name Synonyms
Secondary FlyBase IDs
    References (109)