Human Disease Model Report: retinal disease, rhodopsin-related

General Information

Name

retinal disease, rhodopsin-related

FlyBase ID

FBhh0000219

Disease Ontology Term

retinal disease

Parent Disease

OMIM

Overview

This report encompasses fly models of various retinal diseases in which a rhodopsin gene is implicated as the causative gene. There are multiple rhodopsins in both human and flies, with complicated orthologous relationships; see the FlyBase Gene Groups report RHODOPSINS (FBgg0000070) for information about the Drosophila genes. Four of the human genes (RHO, MIM:180380; OPN1LW, MIM:300822; OPN1SW, MIM:613522; and OPN1MW, MIM:300821) are associated with retinal diseases, including retinitis pigmentosa, color blindness, and night blindness. The Drosophila rhodopsin ninaE has been used in several studies to model retinal disease; classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for this gene.

None of the human rhodopsins that have been implicated in retinal disease has been introduced into flies. A UAS construct of the human gene most closely related to nina, Hsap\OPN4, has been introduced into flies; this gene has not been implicated in disease in human and has not been studied in the context of this disease model.

A mutational lesion of Dmel\ninaE analogous to a variant of the human gene RHO implicated in a form of retinitis pigmentosa has been studied. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): P37H in the fly ninaE gene (corresponds to P23H in the human RHO gene). See the human disease model report for retinitis pigmentosa 4 (FBhh0000199).

In animals carrying null mutations of Dmel\ninaE, the adult compound eye does not develop normally. There are defects in the rhabdomeres of photoreceptor cells R1-R6; progressive retinal degeneration is observed. Phenotypic assays using the fly gene have allowed characterization of genetic interactions. Physical interactions of the ninaE protein product have been described; see below and in the FlyBase gene report for ninaE.

[updated Apr. 2020 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: retinal disease, rhodopsin-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

External links

Gene2Function (human gene): RHO
Gene Cards: RHO
MedlinePlus (condition): Retinitis pigmentosa
MedlinePlus (condition): Autosomal dominant congenital stationary night blindness
MedlinePlus (condition): Color vision deficiency
MedlinePlus (gene): RHO
MARRVEL (human gene): RHO
NCBI (Entrez) gene: RHO; rhodopsin

Disease synonyms

Related Diseases

Related human health report(s)

retinal degeneration, excessive endocytosis of rhodopsin

retinal disease, inherited (fly models overview)

retinitis pigmentosa 4

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

RHO; rhodopsin

D. melanogaster ortholog (based on DIOPT)

Dmel\ninaE

(DIOPT, 2013-)

Dmel\Rh6

(DIOPT, 2013-)

Comments on ortholog(s)

Many to many: both humans and flies have multiple rhodopsin and opsin genes; Dmel\ninaE and Dmel\Rh6 are the best hits for human RHO and several other human genes. RHO and Dmel\ninaE share an extracellular amino domain not found in all rhodopsins.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\ninaE

Gene Snapshot

neither inactivation nor afterpotential E (ninaE) encodes a protein that plays a major role in light detection and vision. It is the rhodopsin expressed in the largest class of photoreceptors in the adult retina. The stimulation by light of the product of ninaE induces G-protein signaling activation, the opening of the channels encoded by trp and trpl and photoreceptor cell membrane depolarization. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Ortholog of human genes OPN4 (reciprocal best hit); lower-scoring ortholog of OPN1LW, RHO and multiple other human opsin genes (multiple Drosophila to multiple human). Dmel\ninaE shares 27-34% identity and 46-51% similarity with these human 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 (15 groups)

ninaE

protein-protein

Interacting group

Assay

References

ninaE - Arr2

cosedimentation in solution, western blot, inferred by author, proximity-dependent biotin identification, anti bait coimmunoprecipitation, affinity technology, autoradiography, cosedimentation

(Feizy et al., 2024, Kristaponyte et al., 2012, Wang et al., 2009, Acharya et al., 2008, Iakhine et al., 2004, Alloway et al., 2000, Alloway and Dolph, 1999)

ninaE - Cnx99A

anti bait coimmunoprecipitation, western blot, pull down

(Chen et al., 2015, Rosenbaum et al., 2006)

ninaE - Edem2

anti tag coimmunoprecipitation, anti tag western blot

(Kang and Ryoo, 2009)

ninaE - Hsc70-3

pull down, western blot

(Chen et al., 2015)

ninaE - inaD

pull down, autoradiography, anti bait coimmunoprecipitation, western blot

(Xu et al., 1998)

ninaE - ninaA

pull down, western blot

(Baker et al., 1994)

ninaE - PAPLA1

anti tag coimmunoprecipitation, western blot

(Kunduri et al., 2014)

ninaE - Rac2

anti tag coimmunoprecipitation, western blot

(Elsaesser et al., 2010)

ninaE - sip3

anti tag coimmunoprecipitation, anti tag western blot

(Kang and Ryoo, 2009)

ninaE - tadr

pull down, western blot

(Ni et al., 2008)

ninaE - trp

anti bait coimmunoprecipitation, western blot

(Chevesich et al., 1997)

ninaE - Tsp42Ej

anti bait coimmunoprecipitation, western blot

(Xu et al., 2004)

ninaE - Xport-A

western blot, anti bait coimmunoprecipitation

(Rosenbaum et al., 2011)

ninaE - Xport-B

pull down, western blot

(Chen et al., 2015)

RNA-protein

Interacting group

Assay

References

ninaE - Fmr1

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Wang et al., 2017)

Alleles Reported to Model Human Disease (Disease Ontology) (24 alleles)

ninaE

Models Based on Experimental Evidence ( 22 )

Allele

Disease

Evidence

References

ninaE¹⁷

model of retinitis pigmentosa 4

CEA

(Galy et al., 2005)

CEA with ninaE^P37H

(Galy et al., 2005)

ninaE^D1

model of retinitis pigmentosa

CEA

(Griciuc et al., 2010)

model of retinal degeneration

CEA

(Lee et al., 2011)

ninaE^E194K

model of retinitis pigmentosa

CEA

(Colley et al., 1995)

ninaE^G119E

model of retinitis pigmentosa

CEA

(Colley et al., 1995)

ninaE^G195S

model of retinitis pigmentosa

CEA

(Colley et al., 1995)

ninaE^G299E

model of retinitis pigmentosa

CEA

(Colley et al., 1995)

ninaE^G69D

model of retinitis pigmentosa

CEA

(Park et al., 2020, Huang et al., 2018, Kang and Ryoo, 2009, Ryoo et al., 2007, Colley et al., 1995)

model of retinitis pigmentosa 4

CEC

(Park et al., 2023, Zhao et al., 2023)

model of retinal disease

CEA

(Xu et al., 2020)

ninaE^S95F

model of retinitis pigmentosa

CEA

(Colley et al., 1995)

ninaE^US6275

model of retinitis pigmentosa

CEA

(Colley et al., 1995)

ninaE^W116stop

model of retinitis pigmentosa

CEA

(Colley et al., 1995)

ninaE^W209stop

model of retinitis pigmentosa

CEA

(Colley et al., 1995)

ninaE^{W313stop.1109}

model of retinitis pigmentosa

CEA

(Colley et al., 1995)

ninaE^{W313stop.1110}

model of retinitis pigmentosa

CEA

(Colley et al., 1995)

ninaE^P37H

model of retinitis pigmentosa

CEA

(Griciuc et al., 2010)

CEA with ninaE¹⁷

(Griciuc et al., 2014)

model of retinitis pigmentosa 4

CEA

(Galy et al., 2005)

CEA with ninaE¹⁷

(Galy et al., 2005)

ninaE^{P37H.Tag:HSV-1-gD}

model of retinitis pigmentosa 4

CEA

(Galy et al., 2005)

ninaE^G69D.UAS

model of retinitis pigmentosa

CEA

(Kang et al., 2017, Chow et al., 2016)

model of retinal disease

CEA

(Kang et al., 2012)

ninaE^G69D.GMR

model of retinitis pigmentosa

CEA

(Huang et al., 2018)

ninaE^G69D.UAS.cXa

model of retinitis pigmentosa

CEA

(Xie et al., 2021)

ninaE^{G69D.UAS.Tag:MYC}

model of retinal disease

CEA

(Xu et al., 2020)

ninaE^P37H.UAS.cXa

model of retinal disease

CEA

(Xu et al., 2020)

ninaE^P37H.UAS

model of retinitis pigmentosa 4

CEC

(Park et al., 2023)

ninaE^P37H.GMR

model of retinitis pigmentosa 4

CEC

(Park et al., 2023)

Modifiers Based on Experimental Evidence ( 11 )

Allele

Disease

Interaction

References

ninaE¹⁷

ameliorates retinitis pigmentosa

modeled by ninaE^P37H

(Griciuc et al., 2010)

DOES NOT ameliorate photosensitive epilepsy

modeled by Cpes^KO

(Kunduri et al., 2018)

ninaE^D1

model of retinitis pigmentosa

is ameliorated by TER94^26-8

(Griciuc et al., 2010)

model of retinal degeneration

is ameliorated by Arl1^GD6768

(Lee et al., 2011)

ninaE^G69D

model of retinitis pigmentosa

is NOT ameliorated by hiro^UAS.Tag:V5

(Huang et al., 2018)

is exacerbated by hiro^F1

(Huang et al., 2018)

is exacerbated by Xbp1^k13803

(Ryoo et al., 2007)

is ameliorated by sip3^UAS.Tag:MYC

(Kang and Ryoo, 2009)

is ameliorated by Herp^GD981

(Kang and Ryoo, 2009)

is ameliorated by Edem2^UAS.Tag:MYC

(Kang and Ryoo, 2009)

is ameliorated by Usp14^UAS.Tag:HA

(Park et al., 2020)

model of retinal disease

is ameliorated by Smg5^UAS.ORF

(Xu et al., 2020)

is ameliorated by Hsap\RNF185^GMR.cXa

(Xu et al., 2020)

is ameliorated by Hsap\RNF5^UAS.cXa

(Xu et al., 2020)

is ameliorated by Hsap\SYVN1^UAS.cXa

(Xu et al., 2020)

is ameliorated by sip3^UAS.Tag:MYC

(Xu et al., 2020)

is ameliorated by sordd1^G757

(Xu et al., 2020)

is ameliorated by sordd1^UAS.cXa

(Xu et al., 2020)

is ameliorated by sordd2^EY20019

(Xu et al., 2020)

is ameliorated by sordd2^UAS.cXa

(Xu et al., 2020)

model of retinitis pigmentosa 4

is ameliorated by PEK^trp.PZ

(Zhao et al., 2023)

is ameliorated by ref(2)P^m.CRISPR

(Zhao et al., 2023)

ninaE^StoA

exacerbates retinal disease

modeled by norpA^P24

(Kristaponyte et al., 2012)

ninaE^P37H

model of retinitis pigmentosa

is ameliorated by ninaE¹⁷

(Griciuc et al., 2010)

is ameliorated by TER94^26-8

(Griciuc et al., 2010)

is ameliorated by TER94^k15502

(Griciuc et al., 2010)

model of retinitis pigmentosa 4

is ameliorated by BacA\p35^UAS.cHa

(Galy et al., 2005)

ninaE^G69D.UAS

model of retinitis pigmentosa

is exacerbated by Gcn2^KK103566

(Kang et al., 2017)

is exacerbated by fred^KK103938

(Chow et al., 2016)

is exacerbated by lola^KK110256

(Chow et al., 2016)

is exacerbated by BBS9^KK102315

(Chow et al., 2016)

is exacerbated by Prosap^KK101537

(Chow et al., 2016)

is exacerbated by Vajk2^KK112024

(Chow et al., 2016)

is exacerbated by hppy^KK101460

(Chow et al., 2016)

is ameliorated by Cdk5^KK109344

(Chow et al., 2016)

is ameliorated by Adgf-D^KK104007

(Chow et al., 2016)

is ameliorated by CG31468^KK110989

(Chow et al., 2016)

is exacerbated by CG2004^GD9700

(Chow et al., 2016)

model of retinal disease

is ameliorated by Cdk5^GD13840

(Kang et al., 2012)

is ameliorated by Diap1^EY00710

(Kang et al., 2012)

is exacerbated by Mekk1^EY02276

(Kang et al., 2012)

is ameliorated by Mekk1^Ur36

(Kang et al., 2012)

is ameliorated by sip3^EY11980

(Kang et al., 2012)

ninaE^G69D.GMR

model of retinitis pigmentosa

is ameliorated by sip3^UAS.Tag:MYC

(Huang et al., 2018)

ninaE^{G69D.UAS.Tag:MYC}

model of retinal disease

is ameliorated by sordd1^UAS.cXa

(Xu et al., 2020)

is ameliorated by sordd2^UAS.cXa

(Xu et al., 2020)

ninaE^P37H.UAS.cXa

model of retinal disease

is ameliorated by sordd1^UAS.cXa

(Xu et al., 2020)

is ameliorated by sordd2^UAS.cXa

(Xu et al., 2020)

ninaE^P37H.GFP

model of retinitis pigmentosa 4

is exacerbated by Prosβ1^HMS00139

(Zhao et al., 2023)

is ameliorated by eIF4G1^HMS00762

(Zhao et al., 2023)

ninaE^P37H.UAS

model of retinitis pigmentosa 4

is ameliorated by wg^KK108857

(Park et al., 2023)

is ameliorated by CG12362^KK111335

(Park et al., 2023)

is ameliorated by Diap1^UAS.ORF

(Park et al., 2023)

is ameliorated by Erasp^KK105798

(Park et al., 2023)

is exacerbated by Ire1^GD3071

(Park et al., 2023)

is ameliorated by Kpc2^KK101215

(Park et al., 2023)

is ameliorated by Lpt^KK107099

(Park et al., 2023)

is ameliorated by pira^KK100639

(Park et al., 2023)

is ameliorated by pygo^KK108114

(Park 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

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

ninaE^G69D.UAS.cXa

P{UAS-Rh1^G69D.X}

ninaE^{G69D.UAS.Tag:MYC}

ninaE^{P37H.Tag:HSV-1-gD}

P{ninaE.2747.P37H.hsv}

ninaE^G69D.GMR

P{GMR-ninaE.G69D}

w^*; CyO/wg^Sp-1; P{GMR-ninaE.G69D}3/TM6B, Tb¹

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

ninaE^GD693

P{GD693}

w¹¹¹⁸; P{GD693}v44178

ninaE^JF01438

P{TRiP.JF01438}

y¹ v¹; P{TRiP.JF01438}attP2

ninaE^JF01439

P{TRiP.JF01439}

y¹ v¹; P{TRiP.JF01439}attP2

ninaE^NIG.4550R

P{NIG.4550R}

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

ninaE^US6275

ethyl methanesulfonate

w^*; ninaE^US6275/TM6B, Tb⁺

ninaE^G299E

ethyl methanesulfonate

ninaE^D1

ethyl methanesulfonate

ninaE^G69D

ethyl methanesulfonate

w^*; ninaE^G69D/TM6B, Tb¹

ninaE¹⁷

loss of function allele

gamma ray

w^*; sr¹ ninaE¹⁷ e^s

ninaE^G195S

ethyl methanesulfonate

ninaE^{W313stop.1109}

ethyl methanesulfonate

ninaE^W116stop

ethyl methanesulfonate

ninaE^G119E

ethyl methanesulfonate

w^*; ninaE^G119E/TM3, Sb¹

ninaE¹¹

amorphic allele - genetic evidence

ethyl methanesulfonate

ninaE¹

loss of function allele

ethyl methanesulfonate

w^*; ort¹ ninaE¹

ninaE^{W313stop.1110}

ethyl methanesulfonate

ninaE^W209stop

ethyl methanesulfonate

ninaE^E194K

ethyl methanesulfonate

ninaE¹³

amorphic allele - genetic evidence

ethyl methanesulfonate

ninaE^S95F

ethyl methanesulfonate

w^*; ninaE^S95F/TM6B, Tb⁺

References (23)

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