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General Information
Name
tauopathies, MAPT-related
FlyBase ID
FBhh0000101
Disease Ontology Term
Parent Disease
OMIM
Overview

A number of inherited neurodegenerative disorders are associated with aggregation of tau protein in the brain. This report describes fly disease models using the human MAPT gene (microtubule-associated protein tau) and the orthologous Drosophila tau gene. For the fly gene, overexpression UAS-tau alleles, RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated; an amorphic Dmel\tau allele has been created via gene targeting and recombination.

Many different UAS constructs of the human Hsap\MAPT gene have been introduced into flies, including wild-type MAPT and genes carrying mutational lesions implicated in frontotemporal dementia (FTD); constructs expressed specifically in the eye have also been generated. Heterologous rescue (functional complementation) is observed for some aspects of the loss-of-function phenotypes described for an RNAi construct that targets Dmel\tau. Phenotypic assays using the human gene have allowed characterization of genetic interactions with candidate fly genes and transgenic human genes.

Variant(s) implicated in human disease tested (as transgenic human gene, MAPT): the variant forms G272V (G589V), P301L (P618L), V337M (V654M), S352L (S669L) and R406W (R723W) have been introduced into flies. These variants are implicated in frontotemporal dementia (FTDP-17; FBhh0000111, OMIM:600274); the variant P301L (P618L) is also implicated in progressive supranuclear palsy 1 (PSNP1; FBhh0000113, OMIM:601104). Additional variant(s) implicated in human disease tested (as transgenic human gene, MAPT): the variant forms R5L, S320F, and G389R have been introduced into flies; R5L is implicated in PSNP1; S320F and G389R are postulated to be pathogenic.

RNAi-effected reduction in levels of Dmel\tau using a general GAL4 driver results in larval/pupal lethality; reduction specifically in the developing eye causes progressive neurodegeneration. Genetic and physical interactions of Dmel\tau have been described; see below and in the tau gene report.

See also allele reports for two marker constructs that incorporate Btau\MAPT (bovine tau) sequences, Ecol\lacZUAS.O.Tag:MT(btau) and Avic\GFPUAS.S65T.I167T.Tag:MT(btau).

[updated Feb. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: tauopathies, MAPT-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Tauopathies are a group of diseases which includes frontotemporal dementia (OMIM:600274), progressive supranuclear palsy (OMIM:601104), and Pick disease (OMIM:172700) (from http://www.mayo.edu/research/labs/neurodegenerative-diseases/targeting-tau-treatment-tauopathies). These neurodegenerative diseases are characterized by the pathological aggregation of tau protein in the brain. Symptoms typically observed include changes in personality and behavior, speech and language abnormalities, problems with movement, and eventual cognitive decline (Genetics Home Reference; MAPT gene; 2016.01.11).

Genetics

Mutations in the human gene MAPT (microtubule-associated protein tau) are implicated in multiple diseases classified as tauopathies. [from OMIM:157140; 2016.01.11]

Cellular phenotype and pathology
Molecular information

Microtubule-associated protein tau (MAPT) is one of a large number of proteins in different cell types that coassemble with tubulin in microtubules; MAPT appears to be enriched in axons. [from OMIM:157140; 2016.01.08]

The MAPT protein promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The human MAPT gene undergoes regulated alterative splicing, producing several different protein isoforms. [UniProt:P10636; 2016.01.11]

The accumulation of hyperphosphorylated tau causes the formation of neurofibrillary tangles, a pathological characteristic of tauopathies. [from http://www.mayo.edu/research/labs/neurodegenerative-diseases/targeting-tau-treatment-tauopathies]

External links
Disease synonyms
MAPT-related disorders
MAPT-related tauopathies
tauopathy_MAPT
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 3 human to 1 Drosophila. Three human genes, MAPT, MAP2 and MAP4, are orthologous to the fly gene Dmel\tau.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Molecular function (GO)
    Gene Groups / Pathways
      Comments on ortholog(s)

      Ortholog of human MAPT (reciprocal best hit), MAP2 and MAP4 (1 Drosophila to 3 human). The 3 human proteins are much longer; Dmel\tau aligns to the tubulin-binding domains at the carboxy termini. Within the aligned region, Dmel\tau shares shares 28-33% identity and 44-46% similarity with the 3 human genes.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (4 groups)
        RNA-RNA
        Interacting group
        Assay
        References
        western blot, quantitative reverse transcription pcr
        protein-protein
        Interacting group
        Assay
        References
        affinity technology, western blot, coimmunoprecipitation
        coimmunoprecipitation, western blot, affinity technology
        anti bait coimmunoprecipitation, anti tag western blot
        Alleles Reported to Model Human Disease (Disease Ontology) (73 alleles)
        Models Based on Experimental Evidence ( 7 )
        Modifiers Based on Experimental Evidence ( 5 )
        Models Based on Experimental Evidence ( 62 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 27 )
        Allele
        Disease
        Interaction
        References
        model of  tauopathy
        is ameliorated by Atg1Δ3D
        is ameliorated by S6kUAS.cUa
        is ameliorated by arm1
        is ameliorated by sgg1
        is exacerbated by panUAS.cWa
        is ameliorated by arm4
        is ameliorated by Vap33Δ448
        is exacerbated by Psa06226
        is ameliorated by POLDIP2EY08866
        is exacerbated by spinΔ2b
        model of  tauopathy
        is exacerbated by f+t13
        is ameliorated by Opa1s3475
        is ameliorated by MarfJF01650
        is exacerbated by MarfUAS.cDa
        is ameliorated by Drp1UAS.cDb
        is exacerbated by WASpUAS.cBa
        is exacerbated by sqhAX3
        is exacerbated by zip1
        is exacerbated by Drp1GD10456
        is exacerbated by LamGL00577
        is ameliorated by Kdm3HMJ22328
        is ameliorated by Kdm2KK101783
        is ameliorated by Kdm4AGD9133
        is ameliorated by Kdm4BKK102089
        is ameliorated by sbr1
        is exacerbated by Klc8ex94
        is exacerbated by AmphEY09339
        is exacerbated by ClcDG23206
        is exacerbated by Chc1
        is exacerbated by Chc4
        is ameliorated by Rab26UAS.YFP
        is exacerbated by Rab26GD9927
        is exacerbated by SytβDG10711
        is exacerbated by AmphGD1311
        is exacerbated by p535A-1-4
        is exacerbated by p5311-1B-1
        is exacerbated by SytβJF02593
        is exacerbated by LerpGD306
        is exacerbated by gGD7158
        is exacerbated by SppGD786
        is exacerbated by DabGD4886
        is ameliorated by hepGD1461
        is exacerbated by krzGD8470
        is exacerbated by ttvGD1993
        is ameliorated by TetGD9718
        is exacerbated by Lkb1UAS.cWa
        is exacerbated by cathD1
        model of  tauopathy
        is ameliorated by HDAC6KO
        is ameliorated by CalpB4062
        is ameliorated by twsUAS.cBa
        is exacerbated by hop2
        is ameliorated by CaMKIIGD9506
        is exacerbated by CaMKIIUAS.cKa
        is exacerbated by Klc8ex94
        is ameliorated by gEP514
        is ameliorated by MESR4EP386
        is ameliorated by svrEP356
        is ameliorated by mubEP3108
        model of  tauopathy
        is ameliorated by HDAC6KO
        is exacerbated by Diap1SL
        is ameliorated by αTub84BK40Q
        is ameliorated by αTub84BK40R
        is ameliorated by MycJF01761
        is exacerbated by SmD2GD7741
        is exacerbated by SmD2HMC03839
        is exacerbated by SmEGD13663
        is exacerbated by SmEHMS00074
        is exacerbated by snfJ210
        is exacerbated by LarGD14391
        is exacerbated by bru1GD8699
        is exacerbated by dopGD11940
        is exacerbated by dopGL00220
        is exacerbated by dopJF02778
        is ameliorated by oxtG4946
        is ameliorated by scbEY02806
        is ameliorated by scbEY10270
        is exacerbated by scbJF02696
        is exacerbated by scbPB.UAS
        is ameliorated by Act5CG0010
        is exacerbated by Act5CUAS.GFP
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Selected mammalian transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        amorphic allele - molecular evidence
        ends-out gene targeting
        References (210)