FlyBase Allele Report: Dmel\ninaE[P37H]

General Information

Symbol

Dmel\ninaE^P37H

Species

D. melanogaster

Name

FlyBase ID

FBal0241243

Feature type

allele

Associated gene

Dmel\ninaE

Associated Insertion(s)

Carried in Construct

P{ninaE.2747.P37H}

Also Known As

Rh1^P37H

Key Links

Genomic Maps

JBrowse

Transgenic product class

missense_variant

(Galy et al., 2005)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

missense_variant

(Galy et al., 2005)

Mutagen

in vitro construct

(Galy et al., 2005)

Progenitor genotype

Carried in construct

P{ninaE.2747.P37H}

Cytology

Description

1747bp of mutated ninaE coding sequence and approximately 1kb of ninaE upstream sequence are cloned into CasPer4.

(Galy et al., 2005)

Amino acid replacement: P37H.

(Galy et al., 2005)

Allele components

Component

Use(s)

Regulatory region(s)

ninaE

Encoded product / tool

ninaE

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

point_mutation

3R:19,887,857..19,887,858 [-]

Comment:

Mutation in analogous codon in human RHO implicated in retinitis pigmentosa 4; mutation carried on in vitro construct; site of nucleotide substitution in fly gene and specific disease association inferred by FlyBase curator.

(Galy et al., 2005)

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 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)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of retinitis pigmentosa

is ameliorated by TER94^26-8

(Griciuc et al., 2010)

is ameliorated by TER94^k15502

(Griciuc et al., 2010)

is ameliorated by ninaE¹⁷

(Griciuc et al., 2010)

model of retinitis pigmentosa 4

is ameliorated by BacA\p35^UAS.cHa

(Galy et al., 2005)

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

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Galy et al., 2005)

RHO:p.Pro23His

(FlyBase curators, 2019-)

Variants Synonym(s)

Associated human disease model(s)

External database links

ClinVar: RHO_13013

Comments concerning this variant

Phenotypic Data

Phenotypic Class

Phenotype Manifest In

autophagosome, with ninaE¹⁷

(Griciuc et al., 2014)

endoplasmic reticulum, with ninaE¹⁷

(Griciuc et al., 2014)

eye photoreceptor cell | adult stage | progressive

(Griciuc et al., 2010)

lysosome, with ninaE¹⁷

(Griciuc et al., 2014)

mitochondrion, with ninaE¹⁷

(Griciuc et al., 2014)

multivesicular body, with ninaE¹⁷

(Griciuc et al., 2014)

ommatidium

(Galy et al., 2005)

retina | adult stage | progressive

(Griciuc et al., 2010)

rhabdomere membrane

(Galy et al., 2005)

rhabdomere of eye photoreceptor cell, with ninaE¹⁷

(Griciuc et al., 2014)

rhabdomere R1

(Galy et al., 2005)

rhabdomere R2

(Galy et al., 2005)

rhabdomere R3

(Galy et al., 2005)

rhabdomere R4

(Galy et al., 2005)

rhabdomere R5

(Galy et al., 2005)

rhabdomere R6

(Galy et al., 2005)

Detailed Description

Statement

Reference

Retinal ultrastructure of transgenic ninaE^P37H flies in a ninaE¹⁷ genetic background is similar to that of wild-type, as evidenced by a normal complement of photoreceptor neurons. However, numerous rhabdomeres exhibit structural abnormalities suggesting rhabdomere structural defects in the mutant. Compared with controls, a marked expansion of the endoplasmic reticulum network is observed in mutant photoreceptor neurons. There is also a significant increase in the number of mitochondria in the mutants relative to wild-type. High-resolution images reveal that numerous mitochondria in the mutant flies display structural abnormalities, such as absent or poorly patterned cristae. Compared with wild-type, a strong increase in the number of autophagic vacuoles, multivesicular bodies, and lysosomes is detected in the mutants.

30-day old transgenic ninaE^P37H flies in a ninaE¹⁷ genetic background, unlike control flies, exhibit a blunted electrical response to light stimulation.

(Griciuc et al., 2014)

Expression of ninaE^P37H leads to progressive retinal degeneration, with a dramatic loss of photoreceptor neurons in adults after 20 and 30 days of light exposure, but not at 1 day or when reared in the dark at 30 days; these flies exhibit visual processing defects after 20 days of light exposure, with a highly impaired positive phototaxis response, but no defects in geotaxis; and ninaE^P37H-expressing photoreceptors have a decreased amplitude of photoreceptor depolarization after both 30 and 45 days of light exposure, as compared to controls.

(Griciuc et al., 2010)

ninaE^P37H.+t2747 transgenic rhabdomeres raised under day/night conditions show no signs of photoreceptor degeneration at eclosion. However, at day 2, vacuoles are found in R1 to R6 cytoplasm and they appear slightly mislocalised. These first degeneration signs are due to light exposure during pupal life, because pupae of the same genotype kept in the dark show no cytoplasm defects. Large numbers of R1-R6 photoreceptors degenerate by day 21 post-eclosion while inner photoreceptors (R7 and R8) remain intact. Morphological signs of degeneration such as reduced or absent rhabdomeres are observed by day 14. This phenotype is highly penetrant, because each ommatidium is affected.

ninaE^P37H.+t2747 flies reared in the dark do not display a degenerative phenotype, even after 35 days of post-eclosion. ninaE^P37H.+t2747 photoreceptors, kept under constant light illumination for 24hrs present degenerative signs, such as involution of microvillar rhabdomere membranes. Degenerating photoreceptor cytoplasm also contains a large number of lysosomes and vacuoles.

ninaE^P37H.+t2747 flies exhibit normal phototaxis at day 1, but display strongly reduced phototaxis at day 14. ninaE^P37H.+t2747-induced defects are already detectable at day 7 and flies display intermediate visual activity. Thus, ninaE^P37H.+t2747 eye morphology correlates with visual behaviour.

ninaE^P37H.+t2747 flies display electroretinogram amplitude similar to that of control flies at day 1. With time, however, the amplitude displayed in ninaE^P37H.+t2747 flies gradually decreases compared to controls and by day 56 reaches that of blind flies.

The presence of ninaE^P37H.+t2747 rescues the ERG phenotype of ninaE¹⁷ mutants at day 1 after eclosion. Compared to wild-type transgenes (such as ninaE^WT.+t2747), however, ninaE^P37H.+t2747-ninaE¹⁷ flies display significantly reduced ERG amplitude.

ninaE^P37H.+t2747 ommatidia display several apoptotic features such as dense nuclei, devolution of rhabdomeric membranes and loss of sub-rhabdomeric structures.

(Galy et al., 2005)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Suppressed by

Statement

Reference

ninaE¹⁷, ninaE^P37H has abnormal neurophysiology phenotype, suppressible by Drice^Δ1/Ice[+]

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has abnormal neuroanatomy phenotype, suppressible by Drice^Δ1/Ice[+]

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has abnormal neurophysiology phenotype, suppressible by hid^A206/W[+]

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has abnormal neurophysiology phenotype, suppressible by Dronc⁵¹/Nc[+]

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has abnormal neuroanatomy phenotype, suppressible by Dronc⁵¹/Nc[+]

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has abnormal neurophysiology phenotype, suppressible by Ark[+]/Dark⁸²

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has abnormal neuroanatomy phenotype, suppressible by Ark[+]/Dark⁸²

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has abnormal neurophysiology phenotype, suppressible by Traf4[+]/Traf4^ex1

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has abnormal neuroanatomy phenotype, suppressible by Traf4[+]/Traf4^ex1

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has abnormal neurophysiology phenotype, suppressible by bsk¹/bsk[+]

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has abnormal neuroanatomy phenotype, suppressible by bsk¹/bsk[+]

(Griciuc et al., 2014)

ninaE^P37H has abnormal neuroanatomy | adult stage | progressive phenotype, suppressible by TER94[+]/TER94^26-8

(Griciuc et al., 2010)

ninaE^P37H has decreased cell number | adult stage | progressive phenotype, suppressible by TER94[+]/TER94^26-8

(Griciuc et al., 2010)

ninaE^P37H has abnormal phototaxis | adult stage phenotype, suppressible by TER94[+]/TER94^26-8

(Griciuc et al., 2010)

ninaE^P37H has abnormal neuroanatomy | adult stage | progressive phenotype, suppressible by TER94[+]/TER94^k15502

(Griciuc et al., 2010)

ninaE^P37H has decreased cell number | adult stage | progressive phenotype, suppressible by TER94[+]/TER94^k15502

(Griciuc et al., 2010)

ninaE^P37H has abnormal phototaxis | adult stage phenotype, suppressible by TER94[+]/TER94^k15502

(Griciuc et al., 2010)

ninaE^P37H has abnormal neurophysiology | adult stage phenotype, suppressible by TER94[+]/TER94^26-8

(Griciuc et al., 2010)

ninaE^P37H has abnormal phototaxis phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

ninaE^P37H has increased cell death phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

ninaE^P37H has abnormal neurophysiology phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

ninaE^P37H has abnormal stress response phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

Phenotype Manifest In

Suppressed by

Statement

Reference

ninaE¹⁷, ninaE^P37H has rhabdomere of eye photoreceptor cell phenotype, suppressible by Drice^Δ1/Ice[+]

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has rhabdomere of eye photoreceptor cell phenotype, suppressible by Dronc⁵¹/Nc[+]

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has rhabdomere of eye photoreceptor cell phenotype, suppressible by Ark[+]/Dark⁸²

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has rhabdomere of eye photoreceptor cell phenotype, suppressible by Traf4[+]/Traf4^ex1

(Griciuc et al., 2014)

ninaE¹⁷, ninaE^P37H has rhabdomere of eye photoreceptor cell phenotype, suppressible by bsk¹/bsk[+]

(Griciuc et al., 2014)

ninaE^P37H has retina | adult stage | progressive phenotype, suppressible by TER94[+]/TER94^26-8

(Griciuc et al., 2010)

ninaE^P37H has eye photoreceptor cell | adult stage | progressive phenotype, suppressible by TER94[+]/TER94^26-8

(Griciuc et al., 2010)

ninaE^P37H has retina | adult stage | progressive phenotype, suppressible by TER94[+]/TER94^k15502

(Griciuc et al., 2010)

ninaE^P37H has eye photoreceptor cell | adult stage | progressive phenotype, suppressible by TER94[+]/TER94^k15502

(Griciuc et al., 2010)

ninaE^P37H has rhabdomere R1 phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

ninaE^P37H has rhabdomere R2 phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

ninaE^P37H has rhabdomere R3 phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

ninaE^P37H has rhabdomere R4 phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

ninaE^P37H has rhabdomere R5 phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

ninaE^P37H has rhabdomere R6 phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

ninaE^P37H has rhabdomere membrane phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

ninaE^P37H has ommatidium phenotype, suppressible by Scer\GAL4^GMR.PF/BacA\p35^UAS.cHa

(Galy et al., 2005)

Additional Comments

Genetic Interactions

Statement

Reference

Retinal degeneration and light-response defects are strongly suppressed in ninaE^P37H, ninaE¹⁷, bsk¹/+ flies.

Retinal degeneration and light-response defects are strongly suppressed in ninaE^P37H, ninaE¹⁷, Traf4^ex1/+ flies.

Retinal degeneration and light-response defects are strongly suppressed in ninaE^P37H, ninaE¹⁷, Ark⁸²/+ flies.

Retinal degeneration and light-response defects are strongly suppressed in ninaE^P37H, ninaE¹⁷, Nc⁵¹/+ flies.

ninaE^P37H, ninaE¹⁷, W^hid-A206/+ flies exhibit strong recovery of visual response to light stimulation.

ninaE^P37H, ninaE¹⁷, Ice^Δ1/+ flies show dramatic suppression of retinal degeneration and strong recovery of visual response to light stimulation.

(Griciuc et al., 2014)

TER94^26-8/+ partially suppresses the retinal degeneration and photoreceptor neuron loss after 30 days, but not after 20 days, of light exposure; rescues the visual processing defects after 20 days of light exposure; and rescues the photoreceptor depolarization defect seen in flies expressing ninaE^P37H.

TER94^k15502/+ strongly suppresses the retinal degeneration and photoreceptor neuron loss seen in flies expressing ninaE^P37H at both 20 and 30 days of light exposure; and rescues the visual processing defects seen in these flies at 20 days of light exposure.

(Griciuc et al., 2010)

Xenogenetic Interactions

Statement

Reference

Expression of BacA\p35^Scer\UAS.cHa under the control of Scer\GAL4^GMR.PF fully prevents the light-induced photoreceptor loss encountered in ninaE^P37H.+t2747 mutants. Rhabdomere and nucleus ultrastructure defects are also rescued, along with the phototactic behaviour.

(Galy et al., 2005)

Complementation and Rescue Data

Comments

ninaE¹⁷/+ or ninaE¹⁷/ninaE¹⁷ largely rescues the retinal degeneration and photoreceptor loss, and partially rescues the phototaxis defects seen in flies expressing ninaE^P37H.

(Griciuc et al., 2010)

The presence of ninaE^P37H.+t2747 rescues the ERG phenotype of ninaE¹⁷ mutants at day 1 after eclosion.

(Galy et al., 2005)

Images (0)

Mutant

Wild-type

Stocks (0)

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (2)

Reported As

Symbol Synonym

ninaE^P37H.+t2747

ninaE^P37H

Name Synonyms

Secondary FlyBase IDs

References (5)

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