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General Information
Symbol
Dmel\Nrx-1273
Species
D. melanogaster
Name
FlyBase ID
FBal0241961
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
dnrx273
Key Links
Allele class
Nature of the Allele
Allele class
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

Imprecise excision of P{XP}Nrx-1d08766 results in an approximate 8kb deletion within the Nrx-1 locus, removing most of the coding sequence for the extracellular region of Nrx-1, from the start codon to the fourth LamG domain.

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 ( 1 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Nrx-1273/Df(3R)5C1 transheterozygotes are viable. Nrx-1273 leads to a significant changes in the third instar larval neuromuscular junction compared to controls: a decrease in the number, but not in the area, of synaptic boutons; a significant increase in the active zone density; a significant increase in the total postsynaptic density length; a significant increase in the ruffle density at the synapse; and significant decreases in the subsynaptic reticulum length and density.

Unlike in wild-type, the axon of L4 lamina neuron in Nrx-1273 homozygous as well as Nrx-1Δ83/Nrx-1273 transheterozygous adults is not restricted to a single medulla column but often extends to neighboring columns, although the axons still terminate appropriately in the M4 layer. Similarly, the interstitial and terminal axonal branches of L4 neurons in Nrx-1273 mutant MARCM clones terminate at the correct layers (M2 and M4, respectively) but both are no longer confined to a single column and the mutant axons often bifurcate in M2 or M3 layer with their terminal branches invading adjacent column. In contrast, no morphological abnormalities are observed in the Nrx-1273 L5 lamina neurons. The defective columnar restriction in Nrx-1273 mutant L4 neuron MARCM clones occurs at mid-pupal stage - at 55 hr after puparium formation (APF) the mutant interstitial and terminal branches extend in one direction whereas branches in other directions retract and this trend continues later in pupal development and by late pupal stage (72-80 hr APF) the branches often invade neighboring columns.

Nrx-1273/+ third instar larvae have similar numbers of boutons at the neuromuscular junction compared to wild type; Nrx-1273/Nrx-1273 mutants have significantly fewer boutons than controls.

Third instar neuromuscular junctions of Nrx-1273/Nrx-1Δ83 mutants exhibit a significant Ca[2+]-concentration-dependent reduction in excitatory junction current (EJC) amplitude, and a small but significant reduction in steady-state quantal content, in response to a 1-Hz train of stimulation, as compared to wild type. In response to 40 Hz tetanic nerve stimulation, NMJs in these mutants show a marked activity-dependent reduction in the amplitude of EJCs under 0.5mM Ca[2+] conditions, show rapid synaptic depression with amplitude of evoked currents showing a steeper decline after 8 stimuli under 1.8mM Ca[2+] conditions, and show a significant reduction in steady state EJC and quantal content, but no significant difference in steady state miniature EJC (mEJC), as compared to wild type.

The number of boutons at the neuromuscular junction is significantly reduced compared to wild type in Nrx-1273/Df(3R)5C1 third instar larvae.

Several ultrastructural defects are seen in the Nrx-1273/Df(3R)5C1 boutons compared to controls. The number of active zones per bouton is increased. The normalised width of the subsynaptic reticulum is severely reduced. The total postsynaptic density length per unit perimeter is increased.

Homozygous third instar larval show a reduction in EJP amplitude at the neuromuscular junction compared to controls. mEJP amplitude is not significantly altered. Quantal content is significantly reduced.

Approximately 10% of progeny from Nrx-1273/Df(3R)5C1 die at pupal stages while the remaining progeny survive to adulthood and are fertile.

Nrx-1273 homozygous, Nrx-1273/Nrx-1241 and Nrx-1273/Df(3R)5C1 heterozygous larva exhibit severely impaired behavior in larval stages, being uncoordinated and sluggish.

Nrx-1273 homozygous, Nrx-1273/Nrx-1241 and Nrx-1273/Df(3R)5C1 heterozygous larva exhibit shortened axon branches with fewer boutons. Mutant neuromuscular junction branches often contain long intervening axon stretches devoid of synaptic boutons. These mutants exhibit a 40-60% decrease in bouton number.

Nrx-1273/Df(3R)5C1 mutants exhibit striking structural abnormalities in active zones and postsynaptic densities of type 1b boutons. PRDs and apposed PSDs are over 60% longer in these mutants compared to controls. The number of T bars per bouton is increased by more than 2-fold. The PRD shows signs of detachment from teh PSD, a phenotype rarely seen in wild-type. In Nrx-1273/Df(3R)5C1 mutant synapses, PRDs show bleb-like invaginations at several points, and at these sites the typical electron density of PRDs is lost. The material at the synaptic cleft also appears altered, but no defects are observed at the corresponding sites of the PSDs.

Several synaptic transmission defects are observed in Nrx-1273/Df(3R)5C1 mutants. Evoked synpatic transmission is reduced, as manifested by a small but significant decrease in the amplitude of EJPs. The frequency and amplitude of mEJPs is dramatically increased, suggesting both a pre- and postsynaptic defect. Overall, quantal content is reduced, indicating defective synaptic transmission.

There is a significant decrease in EJP amplitude in Nrx-1273/Df(3R)5C1 mutants are 0.5mM Ca[2+] concentration. This defect is completely restored at 1mM Ca[2+] concentration.

External Data
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Phenotype Manifest In
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Additional Comments
Genetic Interactions
Statement
Reference

Nlg1Δ46, Nrx-1273 double homozygotes show third instar larval neuromuscular junction defects that are similar to those observed in either single mutant, although there are ocasional giant boutons that are laterally elongated with multiple active zones and reduced subsynaptic reticulum; Nrx-1273, Nlg1Δ46 double heterozygotes also present a significant decrease in the number of synaptic boutons at the third instar larval neuromuscular junction, as compared to single heterozygous and wild-type controls.

The decreased number of synaptic boutons at the third instar larval neuromuscular of Nrx-1273 homozygotes is not suppressed by the expression of witScer\UAS.cMa under the control of Scer\GAL4elav.PU.

Nrx-1273 homozygosity does not suppress or enhance the third instar larval neuromuscular junction defects displayed by witB11/witA12 transheterozygotes. Nrx-1273 homozygosity also does not suppress or enhance the decreased number of synaptic boutons at the third instar larval neuromuscular of Mad12/Madk00237 transheterozygotes.

The impaired columnar restriction of L4 lamina neuron axons (which frequently invade adjacent medulla columns) observed in adult flies expressing EphrinHMS01289 under the control of Scer\GAL4GMR31C06 is not worsened further by combination with Nrx-1Δ83/Nrx-1273 (which on its own also causes defects in columnar restriction of the L4 axons).

Syx473/+;Nrx-1273/+ double heterozygotic third instar larvae have significantly fewer boutons at the neuromuscular junction compared to wild type or single heterozygotes. Syx473/Syx473 does not significantly enhance the decrease in bouton number seen in Nrx-1273/Nrx-1273 larvae. Nrx-1273/Nrx-1273 significantly enhances the decrease in bouton number seen in Syx473/Syx473 larvae.

Nlg2CL2/+ ; Nrx-1273/+ double heterozygous third instar larvae have normal neuromuscular junction morphology.

Nlg2CL2/Nlg2CL2 ; Nrx-1273/Df(3R)5C1 double mutant third instar larvae have a significantly reduced number of boutons at the neuromuscular junction, with the reduction being indistinguishable from that seen for each single mutant combination. EJP amplitude is reduced in the double mutants to a similar degree as that seen in each single mutant.

Synaptic overgrowth caused by Nlg1Scer\UAS.cMa overexpression in the muscle (under the control of Scer\GAL4BG487) is suppressed by Nrx-1273.

Overexpression of Nlg1Scer\UAS.cMa in a Nrx-1273 mutant background does not increase bouton number above that of the negative control (Scer\GAL4BG487/Nlg1Scer\UAS.cMa; Nrx-1273/+).

The inhibitory effects of Nlg1Scer\UAS.cMa overexpression on evoked synaptic transmission are suppressed in Nrx-1273 mutants. EJC amplitude is also significantly restored in these flies.

Xenogenetic Interactions
Statement
Reference
Complementation and Rescue Data
Comments

The decreased number of synaptic boutons observed at the Nrx-1273 homozygous third instar larval neuromuscular junction is rescued by the expression of either Nrx-1Scer\UAS.cLa or Nrx-1ΔC.Scer\UAS, but not Nrx-1ΔN.Scer\UAS, under the control of Scer\GAL4elav.PU.

Expression of Nrx-1Scer\UAS.cZa (but not Nrx-1ΔPBD.Scer\UAS or Nrx-1ΔC.Scer\UAS) under the control of Scer\GAL4RapGAP1-OK6 rescues the rapid synaptic depression seen in third instar Nrx-1273/Nrx-1Δ83 mutant NMJs under 1.8mM Ca[2+] conditions, and expression of Nrx-1Scer\UAS.cZa or Nrx-1ΔPBD.Scer\UAS (but not Nrx-1ΔC.Scer\UAS) rescues the reduced mean EJCs, and the reduced quantal content at the steady state seen in third instar Nrx-1273/Nrx-1Δ83 mutant NMJs under 1.8mM Ca[2+] conditions.

Expression of Nrx-1ΔPBD.Scer\UAS or Nrx-1Scer\UAS.cZa under the control of Scer\GAL4RapGAP1-OK6 restores the decreased initial EJC amplitude and the reduced mean EJCs at the steady state observed in third instar Nrx-1273/Nrx-1Δ83 mutant NMJs under 0.5mM Ca[2+] conditions.

Expression of Nrx-1ΔPBD.Scer\UAS under the control of Scer\GAL4RapGAP1-OK6 restores the decreased initial EJC amplitude but not the the reduced mean EJCs at the steady state observed in third instar Nrx-1273/Nrx-1Δ83 mutant NMJs under 0.5mM Ca[2+] conditions.

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Synonyms and Secondary IDs (4)
References (10)