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General Information
Symbol
Dmel\Tsc1Q87X
Species
D. melanogaster
Name
FlyBase ID
FBal0123965
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Allele class
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
point mutation
Nucleotide change:
C24130984T
Reported nucleotide change: Amino acid change:
Q87term | Tsc1-PA
Reported amino acid change:
Q87term
Comment:
Site of nucleic acid difference inferred by FlyBase based on reported amino acid change
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Cytology
Nature of the lesion
Statement
Reference
Nucleotide substitution: C?T.
Amino acid replacement: Q87term.
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 ( 0 )
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 0 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference
Tsc1Q87X homozygous intestinal stem cell (ISC) clones are lost over time. In wild-type clones, approximately 86-100% of ISC clones present on day 4 are maintained on day 14, while almost all Tsc1Q87X homozygous clones present on day 4 are absent on day 14. The remaining ISC clones on day 14 generally contain fewer cells, indicating that the Tsc1Q87X clones are under-proliferative. The mutant ISCs are also larger than in wild-type. The distribution of TUNEL, a marker for fragmented DNA, indicative of apoptosis, shows that Tsc1Q87X mutant ISC clones do not undergo apoptosis. Treatment of Tsc1Q87X ISC clone flies with rapamycin results in increased survival of the mutant ISC clones and rescues the enteroendocrine cell differentiation defects, in contrast to untreated cells. Only approximately 7% of Tsc1Q87X homozygous mutant intestinal stem cell (ISC) clones contain enteroendocrine cells, and later in development, these enteroendocrine cells are lost, indicating that Tsc1 is essential for enteroendocrine cell differentiation.
eyFLP/MARCM-generated clones of Tsc1Q87X result in eye overgrowth.
Tsc1Q87X/Tsc1Q87X mutant clones on the adult thorax exhibit double bristles, missing bristles, patches of bald cuticle, and delay or premature arrest of the cell cycle, as compared to controls.
Tsc1Q87X mutant larvae appear to undergo precocious development.
Head capsule enlarged - bighead phenotype.
Homozygous Tsc1Q87X animals die as 2nd instar larvae. These animals survive until pupation if they are raised on food containing the rapamycin derivative RAD001, at a concentration of 30 μM. Somatic clones of Tsc1Q87X in the developing eye cause strong overgrowth of the eye. The size of ommatidia in clones is increased relative to wild-type.
Eyes carrying homozygous Tsc1Q87X clones are significantly larger than wild-type eyes with a substantial overrepresentation of mutant tissue over wild-type tissue. The individual facets of the eye as well as the interommatidial bristles are significantly larger in the mutant portions of the eye. Mutant ommatidia are larger than adjacent wild-type ommatidia. The cell bodies of individual mutant cells are enlarged, as are the rhabdomeres of mutant photoreceptor cells. In mosaic ommatidia, the larger rhabdomeres are always mutant, indicating that Tsc1 function is cell autonomous. Mutant ommatidia occasionally have missing or extra photoreceptor cells. Ommatidial misrotations are seen near clonal boundaries. Imaginal discs containing homozygous clones are significantly larger than wild type.
External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement
Reference
Tsc1Q87X has visible | somatic clone phenotype, enhanceable by foxo25
Suppressed by
Statement
Reference
Tsc1Q87X has lethal | larval stage phenotype, suppressible | partially by S6k[+]/S6kl-1
Tsc1Q87X has lethal phenotype, suppressible | partially by Tor2L1/Tor[+]
S6k[+]/S6kl-1, Tsc1Q87X has lethal phenotype, suppressible | partially by Tor2L1/Tor[+]
Tor2L1/Tor[+], Tsc1Q87X has lethal phenotype, suppressible | partially by S6k[+]/S6kl-1
NOT suppressed by
Statement
Reference
NOT Enhancer of
Statement
Reference
Tsc1[+]/Tsc1Q87X is a non-enhancer of small body | pupal stage phenotype of S6kl-1
Suppressor of
Statement
Reference
Tsc1Q87X is a suppressor of increased cell growth | somatic clone | nutrition conditional phenotype of Pten117
NOT Suppressor of
Statement
Reference
Tsc1[+]/Tsc1Q87X is a non-suppressor of small body | pupal stage phenotype of S6kl-1
Phenotype Manifest In
Enhanced by
Statement
Reference
Suppressed by
Statement
Reference
NOT suppressed by
Statement
Reference
Other
Additional Comments
Genetic Interactions
Statement
Reference
The introduction of Tsc1Q87X clones into the neighborhood of Pten117 clones reduces the overgrowth phenotype, under starvation conditions. Thus, even when neighboring with a tissue that also has a growth advantage, Pten clones themselves experience competition for common resources.
A Tsc1Q87X mutant clone background results in the gradual loss of Tsc1Q87X NdsRNA.P.Scer\UAS double mutant intestinal stem cell clones from the epithelium, as only 11.3% intestinal stem cell clones are maintained by 21 days after clone induction, compared with a 94.8% maintenance rate for NdsRNA.P.Scer\UAS single mutants. There is no significant increase in apoptosis in these double mutant cells. At 2 weeks after clone induction, when significant numbers of Tsc1Q87X NdsRNA.P.Scer\UAS double mutant intestinal stem cells have been eliminated, many mutant cells have detached from the epithelium and are found in the lumen. Some delaminate as single cells while others delaminate in clusters. Tsc1Q87X NdsRNA.P.Scer\UAS double mutant intestinal stem cell (ISC) clones are larger than wild-type clones. They are Dl-positive, indicating that they are ISC-like, remain diploid, and are negative for the epithelial cell marker nub. Enteroendocrine cell-like tumours are barely observed in these double mutants.
Eyes remain overgrown when Wbp2KK108304 is expressed in Tsc1Q87X-deficient eyes using eyFlp/MARCM.
Unlike either nero1 or Tsc1Q87X mutant clones, Tsc1Q87X nero1 double mutant clones cannot be recovered. Tsc1Q87Xfully suppresses the autophagic defect seen in nero1 mutant animals. However, this epistatic relationship is reveresed in other contexts such as larval growth and developmental timing. Tsc1Q87X mutant larvae appear to undergo precocious development. However, this precocious development is suppressed in Tsc1Q87X nero1 double mutant larvae.
The second instar lethality of homozygous Tsc1Q87X is rescued to early pupal stages in a S6kl-1 homozygous background, however, the larvae are small and severely delayed in development. In contrast, in a S6kl-1/+ background Tsc1Q87X homozygous animals develop to early pupal stages with little developmental delay, and are significantly larger than wild type. The second instar lethality of homozygous Tsc1Q87X is rescued to adulthood (18.5%) or pupal stages (82.5%) by heterozygosity for Tor2L1. The second instar lethality of homozygous Tsc1Q87X is rescued to adulthood (62%) or pupal stages (93%) by heterozygosity for both S6kl-1 and Tor2L1. The rescued animals are slightly larger than wild-type flies, with overall patterning appearing normal. The rescued females are semi-fertile when crossed to wild-type males, whereas the rescued males are fully fertile when crossed to wild-type females. Eye overgrowth caused by somatic clones of Tsc1Q87X in the developing eye and the increase in ommatidia size within the clones are suppressed in homozygous S6kl-1 animals.
Xenogenetic Interactions
Statement
Reference
Complementation and Rescue Data
Comments
Images (0)
Mutant
Wild-type
Stocks (3)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (6)
References (18)