FlyBase Allele Report: Dmel\htt[98E2]

General Information

Symbol

Dmel\htt^98E2

Species

D. melanogaster

Name

FlyBase ID

FBal0241668

Feature type

allele

Associated gene

Dmel\htt

Associated Insertion(s)

Carried in Construct

Also Known As

dhtt-ko, dhtt^ko

Key Links

Allele class

Mutagen

FLPase

Nature of the Allele

Allele class

Mutagen

FLPase

(Zhang et al., 2009)

Progenitor genotype

PBac{WH}htt^f05417

(Zhang et al., 2009)

P{XP}d08071

(Zhang et al., 2009)

Caused by aberration

Df(3R)98E2

Cytology

Description

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).

(Zhang et al., 2009)

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

Variant Molecular Consequences

Associated Sequence Data

DDBJ / EMBL / GenBank

DNA sequence

Protein sequence

UniProtKB/Swiss-Prot

UniProtKB/TrEMBL

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 )

Disease

Evidence

References

model of Huntington's disease

CEA

(Xu et al., 2022)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

exacerbates Huntington's disease

modeled by Hsap\HTT^Q93.ex1.UAS

(Zhang et al., 2009)

Comments on Models/Modifiers Based on Experimental Evidence ( 0 )

Disease-implicated variant(s)

Phenotypic Data

Phenotypic Class

abnormal locomotor behavior | progressive

(Rui et al., 2015)

fertile

(Zhang et al., 2009)

short lived

(Rui et al., 2015, Zhang et al., 2009)

suppressor of variegation, with In(1)y^3P

(Dietz et al., 2015)

suppressor of variegation, with T(2;3)Sb^V

(Dietz et al., 2015)

viable

(Zhang et al., 2009)

Phenotype Manifest In

adult brain | progressive

(Rui et al., 2015)

autolysosome | adult stage | progressive

(Rui et al., 2015)

mitotic spindle | third instar larval stage, with Scer\GAL4^insc.PU

(Godin et al., 2010)

neuroblast | third instar larval stage, with Scer\GAL4^insc.PU

(Godin et al., 2010)

Detailed Description

Statement

Reference

The positional effect variegation (PEV) at the Sb locus caused by T(2;3)Sb^V or at the y locus caused by In(1)y^3P is significantly suppressed by single copy of htt^98E2.

(Dietz et al., 2015)

htt^98E2 homozygous mutants do not show any obvious defects in the morphology or structure of the adult thorax but the climbing ability of aged htt^98E2 mutants is reduced relative to controls and their adult lifespan is shorter. The number of acidic autolysosomes in the brain of htt^98E2 homozygous adults is normal in young individuals but is much reduced in older flies compared to age-matched controls.

The survival of htt^98E2 homozygous mutants upon starvation do not significantly differ from wild-type controls.

(Rui et al., 2015)

htt^98E2 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.

(Godin et al., 2010)

htt^98E2 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.

htt^98E2 larvae show normal crawling behaviour. Analysis of the larval neuromuscular junction in htt^98E2 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. htt^98E2 larvae show normal electrophysiological responses at the neuromuscular junction.

At day 15 after eclosion and earlier, htt^98E2 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 htt^98E2 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 htt^98E2 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 htt^98E2 flies compared to controls. The axonal termini of Scer\GAL4^A307-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.

(Zhang et al., 2009)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

htt^98E2 has short lived phenotype, enhanceable by Scer\GAL4^shot-OK307/Hsap\MAPT^UAS.GFP

(Rui et al., 2015)

htt^98E2 has abnormal locomotor behavior | progressive phenotype, enhanceable by Scer\GAL4^shot-OK307/Hsap\MAPT^UAS.GFP

(Rui et al., 2015)

Suppressed by

Statement

Reference

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2 has short lived phenotype, suppressible by htt^+m22.7/htt[+]

(Rui et al., 2015)

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2 has abnormal locomotor behavior | progressive phenotype, suppressible by htt^+m22.7/htt[+]

(Rui et al., 2015)

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2 has short lived phenotype, suppressible | partially by Hsap\HTT^16Q.FL.UAS/Scer\GAL4^arm.PS

(Rui et al., 2015)

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2 has abnormal locomotor behavior | progressive phenotype, suppressible | partially by Hsap\HTT^16Q.FL.UAS/Scer\GAL4^arm.PS

(Rui et al., 2015)

Enhancer of

Statement

Reference

htt^98E2 is an enhancer of short lived phenotype of Hsap\HTT^Q93.ex1.UAS, Scer\GAL4^elav-C155

(Zhang et al., 2009)

htt^98E2 is an enhancer of abnormal locomotor behavior phenotype of Hsap\HTT^Q93.ex1.UAS, Scer\GAL4^elav-C155

(Zhang et al., 2009)

Phenotype Manifest In

Suppressed by

Statement

Reference

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2 has adult thorax phenotype, suppressible by htt^+m22.7/htt[+]

(Rui et al., 2015)

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2 has adult somatic muscle cell of thorax phenotype, suppressible by htt^+m22.7/htt[+]

(Rui et al., 2015)

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2 has adult thorax phenotype, suppressible | partially by Hsap\HTT^16Q.FL.UAS, Scer\GAL4^shot-OK307

(Rui et al., 2015)

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2 has adult somatic muscle cell of thorax phenotype, suppressible | partially by Hsap\HTT^16Q.FL.UAS, Scer\GAL4^shot-OK307

(Rui et al., 2015)

Enhancer of

Statement

Reference

htt^98E2/htt[+] is an enhancer of adult thorax phenotype of Atg1[+]/Atg1^Δ3D, Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307

(Rui et al., 2015)

htt^98E2/htt[+] is an enhancer of adult somatic muscle cell of thorax phenotype of Atg1[+]/Atg1^Δ3D, Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307

(Rui et al., 2015)

NOT Enhancer of

Statement

Reference

htt^98E2 is a non-enhancer of rhabdomere phenotype of Hsap\HTT^Q93.ex1.UAS, Scer\GAL4^elav-C155

(Zhang et al., 2009)

NOT Suppressor of

Statement

Reference

htt^98E2 is a non-suppressor of rhabdomere phenotype of Hsap\HTT^Q93.ex1.UAS, Scer\GAL4^elav-C155

(Zhang et al., 2009)

Other

Statement

Reference

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2/htt[+], ref(2)P^c03993/ref(2)P[+] has adult thorax phenotype

(Rui et al., 2015)

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2/htt[+], ref(2)P^c03993/ref(2)P[+] has adult somatic muscle cell of thorax phenotype

(Rui et al., 2015)

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2 has adult thorax phenotype

(Rui et al., 2015)

Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2 has adult somatic muscle cell of thorax phenotype

(Rui et al., 2015)

Atg8a^d4/Atg8a[+], Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2/htt[+] has adult thorax phenotype

(Rui et al., 2015)

Atg8a^d4/Atg8a[+], Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2/htt[+] has adult somatic muscle cell of thorax phenotype

(Rui et al., 2015)

Atg13^Δ81/Atg13[+], Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2/htt[+] has adult somatic muscle cell of thorax phenotype

(Rui et al., 2015)

Atg7[+]/Atg7^d77, Hsap\MAPT^UAS.GFP, Scer\GAL4^shot-OK307, htt^98E2/htt[+] has adult somatic muscle cell of thorax phenotype

(Rui et al., 2015)

Hsap\HTT^Q93.ex1.UAS, Scer\GAL4^elav-C155, htt^98E2 has mushroom body phenotype

(Zhang et al., 2009)

Hsap\HTT^Q93.ex1.UAS, Scer\GAL4^elav-C155, htt^98E2 has adult brain phenotype

(Zhang et al., 2009)

Hsap\HTT^Q93.ex1.UAS, Scer\GAL4^elav-C155, htt^98E2 has adult mushroom body beta-lobe phenotype

(Zhang et al., 2009)

Hsap\HTT^Q93.ex1.UAS, Scer\GAL4^elav-C155, htt^98E2 has adult mushroom body alpha-lobe phenotype

(Zhang et al., 2009)

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 htt^98E2 homozygous adults is partially suppressed by expression of Hsap\HTT^{16Q.FL.Scer\UAS} under the Scer\GAL4^arm.PS driver and further worsened by expression of Hsap\MAPT^{Scer\UAS.T:Avic\GFP} under the control of Scer\GAL4^shot-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\HTT^{16Q.FL.Scer\UAS}.

Expression of Hsap\MAPT^{Scer\UAS.T:Avic\GFP} under the control of Scer\GAL4^shot-OK307 in the htt^98E2 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\MAPT^{Scer\UAS.T:Avic\GFP} expressing flies or the htt^98E2 mutants alone and can be rescued by combination with a single copy of htt^+m22.7. Expression of Hsap\MAPT^{Scer\UAS.T:Avic\GFP} in htt^98E2 heterozygous background does not produce any obvious phenotype in the adult thorax, however, when it is expressed in htt^98E2/+;Atg8a^d4/+ double heterozygotes nearly all the adult flies have collapsed thoraces and display loss of skeletal thoracic muscles.

(Rui et al., 2015)

The eye degeneration phenotype caused by expression of Hsap\HD^{Q93.ex1p.Scer\UAS} under the control of Scer\GAL4^elav-C155 is not enhanced in a htt^98E2 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\HD^{Q93.ex1p.Scer\UAS} under the control of Scer\GAL4^elav-C155 is not seen in a htt^98E2 background. The decrease in mobility that is seen as adults expressing Hsap\HD^{Q93.ex1p.Scer\UAS} under the control of Scer\GAL4^elav-C155 as they age is enhanced in a htt^98E2 background. The double mutant flies also show earlier lethality than animals expressing Hsap\HD^{Q93.ex1p.Scer\UAS} under the control of Scer\GAL4^elav-C155 in a wild-type background.

The brains of adults expressing Hsap\HD^{Q93.ex1p.Scer\UAS} under the control of Scer\GAL4^elav-C155 in a htt^98E2 background show a more severe pathology at 5 days of age compared to adults expressing Hsap\HD^{Q93.ex1p.Scer\UAS} under the control of Scer\GAL4^elav-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\HD^{Q93.ex1p.Scer\UAS} under the control of Scer\GAL4^elav-C155 in a wild-type background. The double mutant brains also have larger areas that are devoid of neuronal cells.

(Zhang et al., 2009)

Complementation and Rescue Data

Rescued by

htt^98E2 is rescued by htt^+m22.7

(Rui et al., 2015)

htt^98E2 is rescued by htt^+m22.7

(Zhang et al., 2009)

Comments

The age-dependent loss of climbing ability as well as the reduced lifespan characteristic for htt^98E2 homozygous adults is fully restored by combination with a single copy of htt^+m22.7.

(Rui et al., 2015)

Images (0)

Mutant

Wild-type

Stocks (0)

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (6)

Reported As

Symbol Synonym

DmHTT-Knock out

(Zala et al., 2013)

dhtt-ko

(Xu et al., 2022, Godin et al., 2010, Zhang et al., 2009)

dhtt^ko

(Dietz et al., 2015, Rui et al., 2015)

dhtt^ko #1

(Xu et al., 2022)

htt-ko

(Marquilly et al., 2021)

htt^98E2

Name Synonyms

Secondary FlyBase IDs

References (8)

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