Human Disease Model Report: anxiety modulator(s), genes affecting actin filament stability

General Information

Name

anxiety modulator(s), genes affecting actin filament stability

FlyBase ID

FBhh0001007

Disease Ontology Term

generalized anxiety disorder

Parent Disease

OMIM

Overview

Fly orthologs of candidate anxiety genes found at quantitative trait loci (QTLs) identified from a mouse genetic experiment were screened using the fly wall-following assay (WAFO, see FBhh0001005). Of 17 fly genes test, 4 exhibited alterations in the WAFO assay, including Dmel\tsr and Dmel\tmod. Knockdown of either gene resulted in reduced WAFO (interpreted as decreased anxiety). Both of these genes impact actin filament stability and dynamics; both genes are orthologous to multiple genes in human (see 'Ortholog Information', below).

Human genes Hsap\DSTN (ortholog of Dmel\tsr) and Hsap\TMOD2 and Hsap\TMOD3 (orthologs of Dmel\tmod) have been introduced into flies, but have not been characterized in the context of this disease model.

Both Dmel\tsr and Dmel\tmod have been extensively characterized: RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for both; physical and genetic interactions have been described for both. See below and in the tsr and tmod gene reports.

[updated Apr. 2020 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: anxiety modulator(s), genes affecting actin filament stability

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

CFL1 and CFL2 encode major components of intranuclear and cytoplasmic actin rods; reversibly control actin polymerization and depolymerization in a pH-dependent manner. [Gene Cards, CFL1, CFL2; 2019.04.23]

(FlyBase Curators, 2013-)

DSTN encodes an actin-binding protein that enhances the turnover rate of actin in vivo. [Gene Cards, DSTN; 2019.04.23]

(FlyBase Curators, 2013-)

Members of the tropomodulin family encode actin-regulatory proteins that cap the pointed end of actin filaments, preventing both elongation and depolymerization; the capping activity is dependent on association with tropomyosin. [Gene Cards, TMOD1, TMOD2; 2019.04.23]

(FlyBase Curators, 2013-)

External links

Disease synonyms

Related Diseases

Related human health report(s)

anxiety modulators, fly wall-following model

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (2)

Dmel\tsr

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate-scoring ortholog of human CFL2, DSTN, and CFL1 (2 Drosophila to 3 human). Dmel\tsr shares 36-37% identity and 50-51% similarity with the human genes. (The second orthologous gene in fly is Dmel\CG6873.)

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\tmod

Gene Snapshot

tropomodulin (tmod) encodes an actin/tropomyosin-associated protein involved in Notch signaling regulation. [Date last reviewed: 2019-09-26]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate- to high-scoring ortholog of TMOD1, TMOD2, TMOD3, and TMOD4 (1 Drosophila to 4 human); low-scoring ortholog of human LMOD1, LMOD2, and LMOD3. Dmel\tmod shares 34-37% identity and 55-59% similarity with the human tropomodulin (TMOD) genes.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (27 groups)

tsr

protein-protein

Interacting group

Assay

References

tsr - CG7737

experimental knowledge based

(Guruharsha et al., 2011)

tsr - flr

anti tag coimmunoprecipitation, western blot

(Chu et al., 2012)

tsr - HIP-R

experimental knowledge based

(Guruharsha et al., 2011)

tsr - mbt

enzymatic study, autoradiography

(Menzel et al., 2007)

tsr - Nlg2

pull down, Identification by mass spectrometry, anti tag coimmunoprecipitation, western blot

(Sun et al., 2023)

tsr - Rack1

anti tag coimmunoprecipitation, western blot

(Sun et al., 2023)

tsr - scrib

anti tag coimmunoprecipitation, western blot

(Cervantes-Sandoval et al., 2016)

tsr - Sumo

anti tag coimmunoprecipitation, comigration in sds page, anti tag western blot

(Pirone et al., 2017)

tsr - Synd

experimental knowledge based

(Guruharsha et al., 2011)

tsr - Tango2

experimental knowledge based

(Guruharsha et al., 2011)

tsr - tobi

experimental knowledge based

(Guruharsha et al., 2011)

tsr - yki

proximity ligation assay, fluorescence microscopy, anti tag coimmunoprecipitation, western blot, bimolecular fluorescence complementation

(Skouloudaki et al., 2019)

tmod

protein-protein

Interacting group

Assay

References

tmod - Bsg

experimental knowledge based

(Guruharsha et al., 2011)

tmod - CG3793

experimental knowledge based

(Guruharsha et al., 2011)

tmod - CG7953

experimental knowledge based

(Guruharsha et al., 2011)

tmod - CG8578

experimental knowledge based

(Guruharsha et al., 2011)

tmod - CG30344

experimental knowledge based

(Guruharsha et al., 2011)

tmod - Coq6

experimental knowledge based

(Guruharsha et al., 2011)

tmod - Cyp4ae1

experimental knowledge based

(Guruharsha et al., 2011)

tmod - Drice

experimental knowledge based

(Guruharsha et al., 2011)

tmod - GstZ1

experimental knowledge based

(Guruharsha et al., 2011)

tmod - hiro

experimental knowledge based

(Guruharsha et al., 2011)

tmod - ICA69

experimental knowledge based

(Guruharsha et al., 2011)

tmod - osk

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Hurd et al., 2016)

tmod - Pcyt2

experimental knowledge based

(Guruharsha et al., 2011)

tmod - Swip-1

experimental knowledge based

(Guruharsha et al., 2011)

tmod - Vha68-2

experimental knowledge based

(Guruharsha et al., 2011)

Alleles Reported to Model Human Disease (Disease Ontology) (11 alleles)

tsr

Models Based on Experimental Evidence ( 7 )

Allele

Disease

Evidence

References

tsr^HMS00534

model of nemaline myopathy 7

CEC

(Christophers et al., 2024)

CEA

(Balakrishnan et al., 2020)

tsr^N121

model of alcohol use disorder

CEA with RhoGAP18B¹

(Ojelade et al., 2015)

tsr^N96A

model of nemaline myopathy 7

CEA

(Balakrishnan et al., 2020)

model of autism spectrum disorder

CEA

(Sun et al., 2023)

tsr^S3A.UAS

model of alcohol use disorder

CEA

(Ojelade et al., 2015)

tsr^k05633

model of alcohol use disorder

CEA with RhoGAP18B¹

(Ojelade et al., 2015)

tsr^KK108706

model of nemaline myopathy 7

CEA

(Balakrishnan et al., 2020)

tsr^{V7M.UAS.Tag:HA}

model of nemaline myopathy 7

CEA

(Balakrishnan et al., 2020)

Modifiers Based on Experimental Evidence ( 7 )

Allele

Disease

Interaction

References

tsr^HMS00534

model of nemaline myopathy 7

is ameliorated by PI31^UAS.Tag:HA

(Balakrishnan et al., 2020)

is exacerbated by Prosβ6^1.B.UAS

(Balakrishnan et al., 2020)

tsr^N121

ameliorates hereditary systemic amyloidosis 1

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

(Oliveira da Silva et al., 2020)

exacerbates Huntington's disease

modeled by Hsap\HTT^{128Q.1-231.UAS}

(Onur et al., 2021)

tsr^S3A.UAS

ameliorates Parkinson's disease 1

modeled by Hsap\SNCA^QUAS.cOa

(Sarkar et al., 2021)

tsr^{UAS.Tag:polyHis}

ameliorates tauopathy

modeled by Hsap\MAPT^V337M.UAS

(Fulga et al., 2007)

ameliorates Parkinson's disease 8

modeled by Lrrk^e03680

(Sarkar et al., 2021)

tsr^UAS.cNa

ameliorates Parkinson's disease 1

modeled by Hsap\SNCA^QUAS.cOa

(Sarkar et al., 2021)

tsr^UAS.EGFP

ameliorates autism spectrum disorder

modeled by Nlg2^KO70

(Sun et al., 2023)

tsr^S3A.UAS.EGFP

ameliorates autism spectrum disorder

modeled by Nlg2^KO70

(Sun et al., 2023)

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

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Hsap\DSTN^{UAS.cBa.Tag:HA}

PBac{UAS-hDSTN.HA}

y¹ w^*; PBac{UAS-hDSTN.HA}VK00033

Hsap\DSTN^UAS.Tag:HA

M{UAS-hDSTN.HA}

y¹ w^*; M{UAS-hDSTN.HA}ZH-86Fb

Hsap\TMOD2^UAS.Tag:HA

PBac{UAS-hTMOD2.HA}

y¹ w^*; PBac{UAS-hTMOD2.HA}VK00037

Hsap\TMOD3^UAS.Tag:HA

PBac{UAS-hTMOD3.HA}

y¹ w^*; PBac{UAS-hTMOD3.HA}VK00037

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

PBac{UAS-tsr.S3A.EGFP}

tsr^UAS.cNa

P{UAS-tsr.N}

P{UAS-tsr.N}1.7, y¹ w^*; βTub60D^Pin-1/CyO

tsr^S3A.UAS

P{UAS-tsr.S3A}

P{UAS-tsr.S3A}4.1, y¹ w^*; βTub60D^Pin-1/CyO

tsr^{UAS.Tag:polyHis}

P{UAS-tsr.His}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00534}attP2

w¹¹¹⁸; P{GD9005}v32601

y¹ v¹; P{TRiP.JF01094}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS02283}attP2

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

tsr^k05633

P-element activity

y¹ w^67c23; P{lacW}tsr^k05633/CyO

tsr^N121

loss of function allele

P-element activity

w^*; P{FRT(w^hs)}G13 tsr^N121/CyO

tsr^N96A

loss of function allele

P-element activity

y¹ w^*; P{FRT(w^hs)}G13 tsr^N96A/CyO

tsr^Δ96

loss of function allele

References (3)

Report Sections

Open Close