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General Information
Symbol
Dmel\ninaEP37H
Species
D. melanogaster
Name
FlyBase ID
FBal0241243
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
Rh1P37H
Key Links
Allele class
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
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.

Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Carried in construct
Cytology
Nature of the lesion
Statement
Reference

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

Amino acid replacement: P37H.

Allele components
Product class / Tool use(s)
Regulatory region(s)
Encoded product / tool
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 )
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
This allele represents a human variant implicated in disease.
RHO:p.Pro23His
Variants Synonym(s)
External database links
Comments concerning this variant
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Retinal ultrastructure of transgenic ninaEP37H 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 ninaEP37H flies in a ninaE17 genetic background, unlike control flies, exhibit a blunted electrical response to light stimulation.

Expression of ninaEP37H 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 ninaEP37H-expressing photoreceptors have a decreased amplitude of photoreceptor depolarization after both 30 and 45 days of light exposure, as compared to controls.

ninaEP37H.+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.

ninaEP37H.+t2747 flies reared in the dark do not display a degenerative phenotype, even after 35 days of post-eclosion. ninaEP37H.+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.

ninaEP37H.+t2747 flies exhibit normal phototaxis at day 1, but display strongly reduced phototaxis at day 14. ninaEP37H.+t2747-induced defects are already detectable at day 7 and flies display intermediate visual activity. Thus, ninaEP37H.+t2747 eye morphology correlates with visual behaviour.

ninaEP37H.+t2747 flies display electroretinogram amplitude similar to that of control flies at day 1. With time, however, the amplitude displayed in ninaEP37H.+t2747 flies gradually decreases compared to controls and by day 56 reaches that of blind flies.

The presence of ninaEP37H.+t2747 rescues the ERG phenotype of ninaE17 mutants at day 1 after eclosion. Compared to wild-type transgenes (such as ninaEWT.+t2747), however, ninaEP37H.+t2747-ninaE17 flies display significantly reduced ERG amplitude.

ninaEP37H.+t2747 ommatidia display several apoptotic features such as dense nuclei, devolution of rhabdomeric membranes and loss of sub-rhabdomeric structures.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressed by
Statement
Reference

ninaE17, ninaEP37H has abnormal neuroanatomy phenotype, suppressible by DriceΔ1/Ice[+]

ninaE17, ninaEP37H has abnormal neuroanatomy phenotype, suppressible by Dronc51/Nc[+]

ninaE17, ninaEP37H has abnormal neurophysiology phenotype, suppressible by Ark[+]/Dark82

ninaE17, ninaEP37H has abnormal neuroanatomy phenotype, suppressible by Ark[+]/Dark82

ninaE17, ninaEP37H has abnormal neurophysiology phenotype, suppressible by Traf4[+]/Traf4ex1

ninaE17, ninaEP37H has abnormal neuroanatomy phenotype, suppressible by Traf4[+]/Traf4ex1

ninaE17, ninaEP37H has abnormal neurophysiology phenotype, suppressible by bsk1/bsk[+]

ninaE17, ninaEP37H has abnormal neuroanatomy phenotype, suppressible by bsk1/bsk[+]

ninaEP37H has abnormal phototaxis | adult stage phenotype, suppressible by TER94[+]/TER9426-8

ninaEP37H has abnormal phototaxis | adult stage phenotype, suppressible by TER94[+]/TER94k15502

Phenotype Manifest In
Suppressed by
Statement
Reference

ninaEP37H has retina | adult stage | progressive phenotype, suppressible | partially by TER94[+]/TER9426-8

ninaEP37H has retina | adult stage | progressive phenotype, suppressible | partially by TER94[+]/TER94k15502

Additional Comments
Genetic Interactions
Statement
Reference

Retinal degeneration and light-response defects are strongly suppressed in ninaEP37H, ninaE17, bsk1/+ flies.

Retinal degeneration and light-response defects are strongly suppressed in ninaEP37H, ninaE17, Traf4ex1/+ flies.

Retinal degeneration and light-response defects are strongly suppressed in ninaEP37H, ninaE17, Ark82/+ flies.

Retinal degeneration and light-response defects are strongly suppressed in ninaEP37H, ninaE17, Nc51/+ flies.

ninaEP37H, ninaE17, Whid-A206/+ flies exhibit strong recovery of visual response to light stimulation.

ninaEP37H, ninaE17, IceΔ1/+ flies show dramatic suppression of retinal degeneration and strong recovery of visual response to light stimulation.

TER9426-8/+ 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 ninaEP37H.

TER94k15502/+ strongly suppresses the retinal degeneration and photoreceptor neuron loss seen in flies expressing ninaEP37H 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.

Xenogenetic Interactions
Statement
Reference

Expression of BacA\p35Scer\UAS.cHa under the control of Scer\GAL4GMR.PF fully prevents the light-induced photoreceptor loss encountered in ninaEP37H.+t2747 mutants. Rhabdomere and nucleus ultrastructure defects are also rescued, along with the phototactic behaviour.

Complementation and Rescue Data
Partially rescued by

ninaEP37H is partially rescued by ninaE17

Comments

ninaE17/+ or ninaE17/ninaE17 largely rescues the retinal degeneration and photoreceptor loss, and partially rescues the phototaxis defects seen in flies expressing ninaEP37H.

The presence of ninaEP37H.+t2747 rescues the ERG phenotype of ninaE17 mutants at day 1 after eclosion.

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
ninaEP37H.+t2747
ninaEP37H
Name Synonyms
Secondary FlyBase IDs
    References (5)