FlyBase Allele Report: Hsap\TTR[V30M.UAS.Tag:HA]

General Information

Symbol

Hsap\TTR^{V30M.UAS.Tag:HA}

Species

H. sapiens

Name

FlyBase ID

FBal0283626

Feature type

allele

Associated gene

Hsap\TTR

Associated Insertion(s)

Carried in Construct

P{UAS-TTR.V30M}

Key Links

Transgenic product class

missense_variant

(Berg et al., 2009)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

missense_variant

(Berg et al., 2009)

Mutagen

in vitro construct

(Berg et al., 2009)

Progenitor genotype

Carried in construct

P{UAS-TTR.V30M}

Cytology

Description

UASt regulates expression of Hsap\TTR containing a V30M mutation - the most prevalent mutation associated with familial amyloidotic polyneuropathy. It is codon optimised for Drosophila, and contains the human secretory signal peptide for Hsap\TTR and a C-terminal Tag:HA tag.

(Berg et al., 2009)

Allele components

Component

Use(s)

Regulatory region(s)

UASt

binary expression system - regulatory region

Encoded product / tool

Hsap\TTR

Tagged with

Tag:HA

epitope tag

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 hereditary systemic amyloidosis 1

CEA

(Oliveira da Silva et al., 2020, Berg et al., 2009)

model of polyneuropathy

CEA

(Berg et al., 2009)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of hereditary systemic amyloidosis 1

is ameliorated by Pak¹¹

(Oliveira da Silva et al., 2020)

is ameliorated by Rac1^J11

(Oliveira da Silva et al., 2020)

is ameliorated by Rac2^Δ

(Oliveira da Silva et al., 2020)

is exacerbated by Rho1^72F

(Oliveira da Silva et al., 2020)

is ameliorated by chic²²¹

(Oliveira da Silva et al., 2020)

is ameliorated by tsr^N121

(Oliveira da Silva et al., 2020)

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

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Berg et al., 2009)

TTR:p.Val50Met

(FlyBase curators, 2019-)

Variants Synonym(s)

TTR:p.Val30Met

Associated human disease model(s)

amyloidosis, hereditary systemic 1

External database links

ClinVar: TTR_13417

Comments concerning this variant

Phenotypic Data

Phenotypic Class

Phenotype Manifest In

adult brain, with Scer\GAL4^elav-C155

(Berg et al., 2009)

adult Pdf neuron | third instar larval stage, with Scer\GAL4^GMR.PU

(Oliveira da Silva et al., 2020)

axon | adult stage, with Scer\GAL4^GMR.PU

(Oliveira da Silva et al., 2020)

axon | third instar larval stage, with Scer\GAL4^GMR.PU

(Oliveira da Silva et al., 2020)

eye, with Scer\GAL4^GMR.PU

(Oliveira da Silva et al., 2020)

eye | progressive, with Scer\GAL4^GMR.PU

(Berg et al., 2009)

eye disc | third instar larval stage, with Scer\GAL4^GMR.PU

(Oliveira da Silva et al., 2020)

interommatidial bristle | absent, with Scer\GAL4^GMR.PU

(Oliveira da Silva et al., 2020)

larval brain | third instar larval stage, with Scer\GAL4^GMR.PU

(Oliveira da Silva et al., 2020)

larval Pdf neuron | third instar larval stage, with Scer\GAL4^GMR.PU

(Oliveira da Silva et al., 2020)

ommatidium, with Scer\GAL4^GMR.PU

(Oliveira da Silva et al., 2020)

ommatidium | progressive, with Scer\GAL4^GMR.PU

(Berg et al., 2009)

Detailed Description

Statement

Reference

Expression of Hsap\TTR^{V30M.UAS.Tag:HA} under the control of Scer\GAL4^GMR.PU leads to smaller eyes, with a severe rough phenotype with fused and disordered ommatidia, lack of mechanosensory bristles and with foci of necrotic lesions.

Constitutive or adult specific (in combination with tub-Gal80[ts]) expression of Hsap\TTR^{V30M.UAS.Tag:HA} under the control of Scer\GAL4^GMR.PU leads to a progressive decrease in the climbing ability of adults.

Expression of Hsap\TTR^{V30M.UAS.Tag:HA} under the control of Scer\GAL4^GMR.PU leads to abnormal axonal projections from third instar eye discs into larval brains. It also leads to abnormal axonal arborization of PDF expressing neurons in third instar larvae and adults, as well as larger neuronal area and disorganized spatial arrangement of cell bodies of adult PDF expressing neurons.

(Oliveira da Silva et al., 2020)

Scer\GAL4^elav-C155-mediated expression of Hsap\TTR^{V30M.Scer\UAS.T:Ivir\HA1} reduces median lifespan to 24 days, compared to 32 days in controls.

Scer\GAL4^elav-C155-mediated expression of Hsap\TTR^{V30M.Scer\UAS.T:Ivir\HA1} results in reduced climbing activity compared to controls.

Scer\GAL4^elav-C155-mediated expression of Hsap\TTR^{V30M.Scer\UAS.T:Ivir\HA1} generates extensive vacuolation in the brain of 20 day-old flies compared to controls. Unlike controls, these brains also show a massive amount of large vacuoles - both in the neuropil and the pericerebral fat body.

By day 25 after eclosion, Scer\GAL4^GMR.PU-mediated expression of Hsap\TTR^{V30M.Scer\UAS.T:Ivir\HA1} results in a degenerated eye. Effects include eye collapse, nonsymmetric degeneration of the eye, and areas of fibrillar deposition. There is evidence of vacuole formation and the ommatidia show a curly morphology.

(Berg et al., 2009)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Hsap\TTR^{V30M.UAS.Tag:HA}, Scer\GAL4^GMR.PU has visible | adult stage phenotype, enhanceable by Rho1^72F

(Oliveira da Silva et al., 2020)

Hsap\TTR^{V30M.UAS.Tag:HA}, Scer\GAL4^GMR.PU has abnormal neuroanatomy | third instar larval stage phenotype, enhanceable by Rho1^72F