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General Information
Symbol
Dmel\Rab7Gal4-KO
Species
D. melanogaster
Name
FlyBase ID
FBal0294205
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
rab7Gal4-knock-in
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Cytology
Nature of the lesion
Statement
Reference

The Rab7 open reading frame has been replaced by a cassette containing sequence encoding a GAL4 driver and a Disc\RFP3xP3.PC marker.

Insertion components
TI{GAL4}Rab7Gal4-KO
Product class / Tool use(s)
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
Modifiers Based on Experimental Evidence ( 0 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 

The Charcot-Marie-Tooth 2B disease is a genetically dominant disorder as all patients contain one wild-type copy and one mutant copy of the human Hsap\RAB7A gene. It has been proposed that the mutant forms of Hsap\RAB7A that are seen in Charcot-Marie-Tooth 2B disease patients are gain of function mutations which cause the adult onset neurodegeneration characteristic of the disease. However, studies in a Drosophila model suggest that the neurodegeneration seen in Charcot-Marie-Tooth 2B disease may be caused by loss of normal Hsap\RAB7A function in the patients rather than by the presence of the mutant protein: mutant flies that completely lack function of the Drosophila Rab7 gene in the eye show adult onset neurodegeneration, while flies overexpressing mutant forms of Rab7 which have been identified in Charcot-Marie-Tooth 2B disease patients (the flies express either a mutant form of Hsap\RAB7A or express the equivalent mutations in the Drosophila Rab7 ortholog) do not show neurodegeneration.

Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Rab7GAL4.T:Disc\RFP mutant flies result in lethality at between 50 and 80% of pupal lethality, with no gross morphological abnormalities. Loss of maternal Rab7 causes lethality in fully developed embryos with no obvious developmental defects. Overall brain structure appears normal, and photoreceptor specification and axon path-finding are comparable to wild type.

Eyes composed entirely of Rab7GAL4.T:Disc\RFP mutant photoreceptor cells (generated using eyFLP) appear morphologically normal.

Electroretinogram recordings reveal no defects in the amplitudes of light-evoked responses and synaptic function in Rab7GAL4.T:Disc\RFP mutant eye clones in newly eclosed adults. However by 5 days old, flies raised in constant ambient light show almost complete loss of synaptic function, a phenotype that is not observed in wild type flies. This loss of synaptic function can be fully rescued by raising the flies in the dark. The light-evoked response amplitude remains unchanged in these flies.

The photoreceptors of Rab7GAL4.T:Disc\RFP mutant eye clones in 5 day old flies raised in the light exhibit rhabdomere degeneration and vacuolisation and degeneration of synaptic terminals. This is not seen in either controls or Rab7GAL4.T:Disc\RFP mutant flies raised in the dark.

Electroretinogram recordings from the larval neuromuscular junction of the Rab7GAL4.T:Disc\RFP mutant are indistinguishable from wild type. The frequency and amplitudes of spontaneous single vesicle release events are normal, as are evoked neurotransmission events.

Flies expressing one copy of Rab7Scer\UAS.T:Avic\GFP-YFP.Venus under the control of one copy of Scer\GAL4Rab7.T:Disc\RFP (in a Rab7GAL4.T:Disc\RFP/+ mutant background) are viable and do not display any obvious behavioural defects or altered lifespan. Electroretinogram recordings from the larval neuromuscular junction are indistinguishable from wild type. The frequency and amplitudes of spontaneous single vesicle release events are normal, as are evoked neurotransmission events. As in wild type, no photoreceptor defects, either morphological or functional, are seen in adult flies that have been exposed to 10 days of constant light stimulation.

Flies expressing one copy of Rab7Q67L.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of one copy of Scer\GAL4Rab7.T:Disc\RFP (in a Rab7GAL4.T:Disc\RFP/+ mutant background) are viable and do not display any obvious behavioural defects or altered lifespan. Electroretinogram recordings from the larval neuromuscular junction are indistinguishable from wild type. The frequency and amplitudes of spontaneous single vesicle release events are normal, as are evoked neurotransmission events. As in wild type, no photoreceptor defects, either morphological or functional, are seen in adult flies that have been exposed to 10 days of constant light stimulation.

Flies expressing one copy of Rab7T22N.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of one copy of Scer\GAL4Rab7.T:Disc\RFP (in a Rab7GAL4.T:Disc\RFP/+ mutant background) are viable and do not display any obvious behavioural defects or altered lifespan. Electroretinogram recordings from the larval neuromuscular junction are indistinguishable from wild type. The frequency and amplitudes of spontaneous single vesicle release events are normal, as are evoked neurotransmission events. As in wild type, no photoreceptor defects, either morphological or functional, are seen in adult flies that have been exposed to 10 days of constant light stimulation.

Flies expressing one copy of Rab7K157N.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of one copy of Scer\GAL4Rab7.T:Disc\RFP (in a Rab7GAL4.T:Disc\RFP/+ mutant background) are viable and do not display any obvious behavioural defects or altered lifespan. Electroretinogram recordings from the larval neuromuscular junction are indistinguishable from wild type. The frequency and amplitudes of spontaneous single vesicle release events are normal, as are evoked neurotransmission events. As in wild type, no photoreceptor defects, either morphological or functional, are seen in adult flies that have been exposed to 10 days of constant light stimulation.

Flies expressing one copy of Rab7L129F.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of one copy of Scer\GAL4Rab7.T:Disc\RFP (in a Rab7GAL4.T:Disc\RFP/+ mutant background) are viable and do not display any obvious behavioural defects or altered lifespan. Electroretinogram recordings from the larval neuromuscular junction are indistinguishable from wild type. The frequency and amplitudes of spontaneous single vesicle release events are normal, as are evoked neurotransmission events. As in wild type, no photoreceptor defects, either morphological or functional, are seen in adult flies that have been exposed to 10 days of constant light stimulation.

Flies expressing Rab7N161T.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of one copy of Scer\GAL4Rab7.T:Disc\RFP (in a Rab7GAL4.T:Disc\RFP/+ mutant background) are viable and do not display any obvious behavioural defects or altered lifespan. Electroretinogram recordings from the larval neuromuscular junction are indistinguishable from wild type. The frequency and amplitudes of spontaneous single vesicle release events are normal, as are evoked neurotransmission events. As in wild type, no photoreceptor defects, either morphological or functional, are seen in adult flies that have been exposed to 10 days of constant light stimulation.

Flies expressing one copy of Rab7V162M.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of one copy of Scer\GAL4Rab7.T:Disc\RFP (in a Rab7GAL4.T:Disc\RFP/+ mutant background) are viable and do not display any obvious behavioural defects or altered lifespan. Electroretinogram recordings from the larval neuromuscular junction are indistinguishable from wild type. The frequency and amplitudes of spontaneous single vesicle release events are normal, as are evoked neurotransmission events. As in wild type, no photoreceptor defects, either morphological or functional, are seen in adult flies that have been exposed to 10 days of constant light stimulation.

Defects in synaptic function defects are seen in heterozygous Rab7GAL4.T:Disc\RFP mutant flies that have been raised in constant light for 10 days. The phenotype is not present when flies are raised in the dark and the light-evoked response amplitude is unaffected. Partial loss of rhabdomere structures is seen when heterozygous flies are raised in constant light for either 5 and 10 days.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressed by
Other
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference

Flies expressing one copy of Hsap\RAB7AScer\UAS.T:Avic\GFP-YFP.Venus under the control of one copy of Scer\GAL4Rab7.T:Disc\RFP (in a Rab7GAL4.T:Disc\RFP/+ mutant background) are viable and do not display any obvious behavioural defects or altered lifespan. Electroretinogram recordings from the larval neuromuscular junction are indistinguishable from wild type. The frequency and amplitudes of spontaneous single vesicle release events are normal, as are evoked neurotransmission events. As in wild type, no photoreceptor defects, either morphological or functional, are seen in adult flies that have been exposed to 10 days of constant light stimulation.

Expression of one copy of Hsap\RAB7AScer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the lethality seen in homozygous Rab7GAL4.T:Disc\RFP mutant flies.

Expression of Hsap\RAB7AScer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP partially rescues the progressive synaptic and neuronal degeneration seen in homozygous Rab7GAL4.T:Disc\RFP mutant eye clones after 10 days of constant light stimulation.

Flies expressing Hsap\RAB7AK157N.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of one copy of Scer\GAL4Rab7.T:Disc\RFP (in a Rab7GAL4.T:Disc\RFP/+ mutant background) are viable and do not display any obvious behavioural defects or altered lifespan. Electroretinogram recordings from the larval neuromuscular junction are indistinguishable from wild type. The frequency and amplitudes of spontaneous single vesicle release events are normal, as are evoked neurotransmission events. As in wild type, no photoreceptor defects, either morphological or functional, are seen in adult flies that have been exposed to 10 days of constant light stimulation.

Expression of Hsap\RAB7AK157N.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the lethality seen in homozygous Rab7GAL4.T:Disc\RFP mutant flies.

Expression of Hsap\RAB7AK157N.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP partially rescues the progressive synaptic and neuronal degeneration seen in homozygous Rab7GAL4.T:Disc\RFP mutant eye clones after 10 days of constant light stimulation.

Complementation and Rescue Data
Partially rescued by
Comments

Expression of Rab7Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the lethality seen in homozygous Rab7GAL4.T:Disc\RFP mutant flies.

Expression of Rab7Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the progressive synaptic and neuronal degeneration seen in homozygous Rab7GAL4.T:Disc\RFP mutant eye clones after 10 days of constant light stimulation.

Expression of Rab7Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the dominant defects in synaptic function and rhabdomere structure seen in Rab7GAL4.T:Disc\RFP/+ mutant adults after 5 days of constant light stimulation. A similar level of rescue is seen whether the transgene expresses 0.5x, 1x or >10x the amount of endogenous Rab7 protein.

Expression of Rab7T22N.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP fails to rescue the lethality seen in homozygous Rab7GAL4.T:Disc\RFP mutant flies. Occasional escapers are seen, but these die shortly after emergence.

Expression of Rab7T22N.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP partially rescues the progressive synaptic and neuronal degeneration seen in homozygous Rab7GAL4.T:Disc\RFP mutant eye clones after 10 days of constant light stimulation.

Expression of Rab7Q67L.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the lethality seen in homozygous Rab7GAL4.T:Disc\RFP mutant flies.

Expression of Rab7Q67L.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the progressive synaptic and neuronal degeneration seen in homozygous Rab7GAL4.T:Disc\RFP mutant eye clones after 10 days of constant light stimulation.

Expression of Rab7K157N.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the lethality seen in homozygous Rab7GAL4.T:Disc\RFP mutant flies.

Expression of Rab7K157N.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the progressive synaptic and neuronal degeneration seen in homozygous Rab7GAL4.T:Disc\RFP mutant eye clones after 10 days of constant light stimulation.

Expression of Rab7K157N.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the dominant defects in synaptic function and rhabdomere structure seen in Rab7GAL4.T:Disc\RFP/+ mutant adults after 5 days of constant light stimulation. A similar level of rescue is seen whether the transgene expresses 0.5x, 1x or >10x the amount of endogenous Rab7 protein.

Expression of Rab7L129F.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the lethality seen in homozygous Rab7GAL4.T:Disc\RFP mutant flies.

Expression of Rab7L129F.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the progressive synaptic and neuronal degeneration seen in homozygous Rab7GAL4.T:Disc\RFP mutant eye clones after 10 days of constant light stimulation.

Expression of Rab7L129F.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the dominant defects in synaptic function and rhabdomere structure seen in Rab7GAL4.T:Disc\RFP/+ mutant adults after 5 days of constant light stimulation. A similar level of rescue is seen whether the transgene expresses 0.5x, 1x or >10x the amount of endogenous Rab7 protein.

Expression of Rab7N161T.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the lethality seen in homozygous Rab7GAL4.T:Disc\RFP mutant flies.

Expression of Rab7N161T.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the progressive synaptic and neuronal degeneration seen in homozygous Rab7GAL4.T:Disc\RFP mutant eye clones after 10 days of constant light stimulation.

Expression of Rab7N161T.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the dominant defects in synaptic function and rhabdomere structure seen in Rab7GAL4.T:Disc\RFP/+ mutant adults after 5 days of constant light stimulation. A similar level of rescue is seen whether the transgene expresses 0.5x, 1x or >10x the amount of endogenous Rab7 protein.

Expression of Rab7V162M.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the lethality seen in homozygous Rab7GAL4.T:Disc\RFP mutant flies.

Expression of Rab7V162M.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the progressive synaptic and neuronal degeneration seen in homozygous Rab7GAL4.T:Disc\RFP mutant eye clones after 10 days of constant light stimulation.

Expression of Rab7V162M.Scer\UAS.T:Avic\GFP-YFP.Venus under the control of Scer\GAL4Rab7.T:Disc\RFP rescues the dominant defects in synaptic function and rhabdomere structure seen in Rab7GAL4.T:Disc\RFP/+ mutant adults after 5 days of constant light stimulation. A similar level of rescue is seen whether the transgene expresses 0.5x, 1x or >10x the amount of endogenous Rab7 protein.

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Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (5)
Reported As
Symbol Synonym
Rab7GAL4.T:Disc\RFP
Rab7Gal4-KO
rab7gal4-knock-in
Name Synonyms
Secondary FlyBase IDs
    References (4)