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General Information
Symbol
Dmel\htt98E2
Species
D. melanogaster
Name
FlyBase ID
FBal0241668
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
dhtt-ko, dhttko
Allele class
Mutagen
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Cytology
Nature of the lesion
Statement
Reference

Recombination between the two progenitor insertions has resulted in deletion of the intervening sequence, which deletes the CG9990 gene and 34kb of the 38kb genomic coding region for htt (only the last two exons remain).

Caused by aberration
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 ( 1 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

The positional effect variegation (PEV) at the Sb locus caused by T(2;3)SbV or at the y locus caused by In(1)y3P is significantly suppressed by single copy of htt98E2.

htt98E2 homozygous mutants do not show any obvious defects in the morphology or structure of the adult thorax but the climbing ability of aged htt98E2 mutants is reduced relative to controls and their adult lifespan is shorter. The number of acidic autolysosomes in the brain of htt98E2 homozygous adults is normal in young individuals but is much reduced in older flies compared to age-matched controls.

The survival of htt98E2 homozygous mutants upon starvation do not significantly differ from wild-type controls.

htt98E2 mutants display mitotic spindle defects in third instar larval neuroblasts: in contrast to wild-type controls, a significant proportion of cells show spindles with the angle between centrosomal pole and center of the mira protein crescent higher than the 15[o] and the spindle is also significantly shorter than in controls. The number of neuroblasts in the larval brain is however comparable to wild-type.

htt98E2 animals (Df(3R)98E2 homozygotes in which CG9990 function has been rescued by P{CG9990+t24.7}, referred to as "dhtt-ko") are homozygous viable, develop at a similar rate to wild-type flies and give rise to fertile adults with no discernible morphological abnormalities. The embryonic central nervous system (CNS) and muscles, and the larval muscles, CNS and other imaginal discs all appear normal. The external eye morphology of 40 day old adults is normal, and ommatidia contain the normal number of photoreceptor cells.

htt98E2 larvae show normal crawling behaviour. Analysis of the larval neuromuscular junction in htt98E2 animals show that axonal pathfinding, muscle innervation and overall synapse structure are normal. The number of boutons and of axonal branches is normal as is the organization of the presynaptic microtubule cytoskeleton. htt98E2 larvae show normal electrophysiological responses at the neuromuscular junction.

At day 15 after eclosion and earlier, htt98E2 adults show similar spontaneous locomotion as that of wild-type controls. However, as the mutant flies age, they show a rapidly declining mobility, which is evident by day 25. By day 40, almost all the mutant show severely compromised mobility. The mutant flies also have a shortened adult lifespan, with half of them dying by around day 43 and almost all by day 50.

40-45 day old htt98E2 adults do not show abnormal seizure activity in extracellular recordings from dorsal longitudinal flight muscles in the giant fiber escape pathway. The aged flies also show normal electroretinogram (ERG) responses in the eye at room temperature. At 37[o]C, 1 day old htt98E2 adults show normal ERGs, but 60% of 40-45 day old mutant adults lose light-induced phototransduction and the on/off transients (compared to only 20% of aged controls).

There is a slight reduction in the average size of the mushroom bodies in 40 day old htt98E2 flies compared to controls. The axonal termini of Scer\GAL4A307-labelled neurons have a significantly reduced number of varicosities and branches in the mutant flies compared to controls and the total area occupied by the mutant axonal termini is only about half that of controls.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Phenotype Manifest In
Suppressed by
Enhancer of
Statement
Reference
NOT Enhancer of
Statement
Reference
NOT Suppressor of
Statement
Reference
Other
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference

The age-dependent loss of climbing ability as well as the reduced lifespan characteristic for htt98E2 homozygous adults is partially suppressed by expression of Hsap\HTT16Q.FL.Scer\UAS under the Scer\GAL4arm.PS driver and further worsened by expression of Hsap\MAPTScer\UAS.T:Avic\GFP under the control of Scer\GAL4shot-OK307 in the mutant background. This worsened phenotype can in turn be fully rescued by combination with a single copy of htt+m22.7 and partially rescued by co-expression of Hsap\HTT16Q.FL.Scer\UAS.

Expression of Hsap\MAPTScer\UAS.T:Avic\GFP under the control of Scer\GAL4shot-OK307 in the htt98E2 homozygous mutant background induces prominent collapse of the thorax due to severe loss of the muscles below, these phenotypes are not observed in either the Hsap\MAPTScer\UAS.T:Avic\GFP expressing flies or the htt98E2 mutants alone and can be rescued by combination with a single copy of htt+m22.7. Expression of Hsap\MAPTScer\UAS.T:Avic\GFP in htt98E2 heterozygous background does not produce any obvious phenotype in the adult thorax, however, when it is expressed in htt98E2/+;Atg8ad4/+ double heterozygotes nearly all the adult flies have collapsed thoraces and display loss of skeletal thoracic muscles.

The eye degeneration phenotype caused by expression of Hsap\HDQ93.ex1p.Scer\UAS under the control of Scer\GAL4elav-C155 is not enhanced in a htt98E2 background (Df(3R)98E2 homozygotes in which CG9990 function has been rescued by P{CG9990+t24.7}).

The initial hyperactivity phenotype of adults expressing Hsap\HDQ93.ex1p.Scer\UAS under the control of Scer\GAL4elav-C155 is not seen in a htt98E2 background. The decrease in mobility that is seen as adults expressing Hsap\HDQ93.ex1p.Scer\UAS under the control of Scer\GAL4elav-C155 as they age is enhanced in a htt98E2 background. The double mutant flies also show earlier lethality than animals expressing Hsap\HDQ93.ex1p.Scer\UAS under the control of Scer\GAL4elav-C155 in a wild-type background.

The brains of adults expressing Hsap\HDQ93.ex1p.Scer\UAS under the control of Scer\GAL4elav-C155 in a htt98E2 background show a more severe pathology at 5 days of age compared to adults expressing Hsap\HDQ93.ex1p.Scer\UAS under the control of Scer\GAL4elav-C155 in a wild-type background. The mushroom bodies appear less organised (the characteristic bulged tip of the vertical α-lobes is largely unrecognizable in 95% of cases and the clear separation between the pair of medially projected β-lobes is less distinct and often appears to be merged) and they are reduced in size compared to animals expressing Hsap\HDQ93.ex1p.Scer\UAS under the control of Scer\GAL4elav-C155 in a wild-type background. The double mutant brains also have larger areas that are devoid of neuronal cells.

Complementation and Rescue Data
Comments

The age-dependent loss of climbing ability as well as the reduced lifespan characteristic for htt98E2 homozygous adults is fully restored by combination with a single copy of htt+m22.7.

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Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (4)
Reported As
Symbol Synonym
Name Synonyms
Secondary FlyBase IDs
    References (6)