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General Information
Symbol
Dmel\witA12
Species
D. melanogaster
Name
FlyBase ID
FBal0096773
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Key Links
Allele class
Mutagen
    Nature of the Allele
    Allele class
    Mutagen
    Mutations Mapped to the Genome
     
    Type
    Location
    Additional Notes
    References
    Nucleotide change:

    C4067867T

    Reported nucleotide change:

    C684T

    Amino acid change:

    Q92term | wit-PA; Q92term | wit-PB

    Reported amino acid change:

    ??term

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

    Amino acid replacement: ??term.

    The premature stop codon is before the transmembrane segment.

    Nucleotide substitution: C684T.

    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 ( 0 )
    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

    witA12/witB11 (but not witA12/+) third instar larvae display synaptic undergrowth with fewer mature and satellite boutons at the NMJ than controls.

    witA12 third instar larval C4da neurons do not show any obvious defects in the dendritic arborization, as compared to controls.

    witB11/witA12 transheterozygotes do not reach adulthood and present 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, but not density.

    Third instar larvae heterozygous for witA12 show no significant differences in the number or size of neuromuscular junction boutons compared to wild-type controls.

    Bouton and branch number at the neuromuscular junction of witA12/+ third instar larvae is similar to controls.

    witA12/witB11 mutant third instar larvae do display synaptic undergrowth (reduced number of boutons) at neuromuscular junctions compared to controls.

    witA12/witB11 mutants show a significant reduction in bouton number at neuromuscular junction 4.

    witA12/witunspecified mutants show a significant reduction in bouton number at muscles 6/7 and 4 NMJs compared to controls.

    witA12/witB11 third instar larvae show a significant decrease in bouton number and satellite bouton number at the neuromuscular junction compared to controls.

    witB11/witA12 larvae show a reduction in synaptic terminal size at the neuromuscular junction (NMJ) compared to wild type. The frequency and amplitude of the spontaneous miniature excitatory junctional potential (EJP) at the NMJ are decreased compared to wild type.

    Heterozygotes do not display defects in neuromuscular junction expansion.

    witA12/witB11 animals display a 46% reduction in bouton number at neuromuscular junction 4.

    witA12/witHA3 third instar larvae exhibit neuromuscular junction overgrowth and a reduced number of boutons per muscle surface area in muscle 4 compared to controls. Evoked excitatory junctional potentials (EJPs) and quantal content are reduced compared to controls. The size of the miniature excitatory junctional potentials does not differ from controls.

    witA12/witB11 transheterozygotes exhibit approximately half the number of synaptic boutons as found in wild-type terminals.

    witA12/witB11 third instar larvae display small neuromuscular junctions.

    witA12/witB11 larvae exhibit synaptic undergrowth.

    witA12 heterozygotes do not exhibit any synaptic growth defects.

    aCC/RP2 synaptic current amplitude in witA12/witB11 mutants does not differ from wild-type.

    witA12/witB11 larvae show a decrease in the number of type 1b boutons at muscle 13 compared to wild type.

    The average total bouton number at the neuromuscular junction is decreased in witA12/witB11 larvae compared to controls.

    witA12/witB11 third instar larvae show a reduction in synaptic growth at the neuromuscular junction. The mean bouton number for segment A3, muscle 6/7 is reduced compared to wild type, and fewer satellite boutons are seen in segments A2-A3, muscle 4 than in controls.

    witA12/witB11 mutants exhibit a dramatic reduction in bouton number (64%), branching (80%), and synaptic area (64%).

    witA12/witB11 trans-heterozygous neuromuscular junctions exhibit very low EJP amplitudes and low quantal content, but maintain wild-type level mEJP amplitudes.

    At 25oC less than 0.5% of witA12/witB11 animals escape from the pupal case.

    witA12/witC175 transheterozygous mutants are completely lethal. Approximately 50% of animals survive to the pharate stage. The remaining animals die during larval and early pupal stages. Those animals that do survive to pharate adult stage exhibit the head expansion and abdominal peristaltic movements characteristic of normal pre-eclosion behaviour, but do not rupture nor escape from the pupal case. Many pharate adults show a bend in the femur or tibia, the phenotype being more pronounced in the metathoracic leg. A small fraction of the animals also exhibit truncations of the tarsal segments. The general organisation of the nervous system in these mutants is essentially normal. witA12/witC175 mutant larvae exhibit dramatically reduced transmitter release from presynaptic terminals when the excitatory junctional current (EJC) of body wall muscles examined. The amplitude of EJCs at 0.8 mM Ca2+ is significantly reduced in mutants. Most nerve stimuli fail to evoke transmitter release at low extracellular Ca<up>2+</up> in mutants. Cooperativity is unaffected in mutants. The amplitude of miniature excitatory junction potentials (mEJPs) is not significantly altered in mutants. The number of synaptic boutons seen in ventral longitudinal muscles 6 and 7 in witA12/witC175 third instar larvae, are about half that seen in wild-type animals, when corrected for muscle size the number of synaptic boutons seen is about 70% of wild-type. Although synapse size and bouton number are reduced in mutants, the overall percentage reduction is not proportionately as severe as the reduction in EJC magnitude. Bouton size and overall synaptic structure appear normal. However there is a dramatic alteration in the morphology of the active zone. The pre- and postsynaptic membranes are no longer closely aligned. The presynaptic membrane detaches completely from the postsynaptic membrane, forming large curvatures bending toward the cytosol of nerve terminals. Such membrane detachments also occur in areas near the active zones. However presynaptic membranes do not separate from postsynaptic membranes.

    witA12/witB11 larvae show a significant decrease in bouton number at the neuromuscular junction.

    External Data
    Interactions
    Show genetic interaction network for Enhancers & Suppressors
    Phenotypic Class
    Enhanced by
    NOT Enhanced by
    Suppressed by
    NOT suppressed by
    Statement
    Reference
    Enhancer of
    Statement
    Reference

    witA12/wit[+] is an enhancer of abnormal neuroanatomy phenotype of Impβ1170

    NOT Enhancer of
    Suppressor of
    Statement
    Reference

    witA12/wit[+] is a suppressor of abnormal neuroanatomy | larval stage phenotype of Acsl05847/AcslKO

    witA12/wit[+] is a suppressor of abnormal neuroanatomy phenotype of Scer\GAL4C57, WASpGD1559

    witA12/wit[+] is a suppressor | partially of abnormal neuroanatomy phenotype of spictmut

    NOT Suppressor of
    Other
    Phenotype Manifest In
    Enhanced by
    Statement
    Reference
    NOT Enhanced by
    Statement
    Reference

    witB11/witA12 has synapse phenotype, non-enhanceable by WASpGD1559/Scer\GAL4C57

    Suppressed by
    Statement
    Reference
    NOT suppressed by
    Statement
    Reference

    witB11/witA12 has synapse phenotype, non-suppressible by WASpGD1559/Scer\GAL4C57

    witA12 has NMJ bouton | third instar larval stage phenotype, non-suppressible by nwk1

    Enhancer of
    NOT Enhancer of
    Statement
    Reference
    Suppressor of
    Statement
    Reference

    witA12/wit[+] is a suppressor of NMJ bouton | third instar larval stage phenotype of cpxSH1

    witA12/wit[+] is a suppressor of NMJ bouton | increased number phenotype of S6KL140

    witA12/wit[+] is a suppressor of neuromuscular junction phenotype of Acsl05847/AcslKO

    witA12/wit[+] is a suppressor of NMJ bouton | increased number phenotype of Acsl05847/AcslKO

    witA12/wit[+] is a suppressor of A2 neuron phenotype of Acsl05847/AcslKO

    witA12/wit[+] is a suppressor of A3 neuron phenotype of Acsl05847/AcslKO

    witA12/wit[+] is a suppressor of adult brain | progressive phenotype of spartin1/Df(3R)110

    witA12/wit[+] is a suppressor of bouton phenotype of Cip4NIG.15015R, Scer\GAL4C57

    witA12/wit[+] is a suppressor of neuromuscular junction phenotype of Scer\GAL4C57, WASpGD1559

    witA12/wit[+] is a suppressor of bouton phenotype of Scer\GAL4C57, WASpGD1559

    witA12/wit[+] is a suppressor of bouton | increased number phenotype of spink09905/spin10403

    NOT Suppressor of
    Other
    Additional Comments
    Genetic Interactions
    Statement
    Reference

    Expressing Rac1N17.UAS under the control of Scer\GAL4elav-C155 in a witA12 background results in significantly fewer satellite boutons, but a similar number of mature synaptic boutons as controls at the NMJ of third instar larvae. The number of both bouton types is significantly reduced when expression is driven in a witA12/witB11 background.

    The third instar larval neuromuscular junction defects observed in witB11/witA12 transheterozygotes is not suppressed or enhanced by either Nrx-1273 or Nlg1Δ46 homozygosity.

    The third instar larval neuromuscular junctions of individuals that both express Nrx-1Scer\UAS.cLa under the control of Scer\GAL4elav.PU and are witB11/witA12 transheterozygous show a decrease in the number of synaptic boutons similar to what is observed in witB11/witA12 transheterozygotes, rather than the increase induced by the expression of Nrx-1Scer\UAS.cLa.

    The increased bouton and satellite bouton number characteristic for third instar larvae expressing two copies of Nlg4Scer\UAS.cZa under the control of Scer\GAL4RapGAP1-OK6 is suppressed by combination with a single copy of witA12.

    Although none of the larvae heterozygous for either Nlg4KO10 or witA12 display any significant difference in the number or size of boutons on neuromuscular junctions compared to controls, witA12,Nlg4KO10 double heterozygotes show reduced bouton number and increased bouton size.

    Syx473/+;witA12/+ double heterozygotic third instar larvae do not show significant differences in bouton number at the neuromuscular junction compared to wild type or single heterozygotes.

    witA12/+ significantly suppresses the increases in mature boutons and branch number seen at the neuromuscular junction of Fmr1Δ113M/+ third instar larvae (though bouton and branch number is significantly higher in Fmr1Δ113M/+;witA12/+ larvae than witA12/+ larvae). witA12/witB11 fully suppresses the increase in mature boutons and branch number seen at the neuromuscular junction of Fmr1Δ113M/+ third instar larvae (branch number is significantly higher in witA12/witB11 larvae than Fmr1Δ113M/+;witA12/witB11 larvae).

    Introducing a single copy of witA12 into the cpxSH1 mutant background also rescues the synaptic overgrowth but not the elevated minis, combination with witA12/witB11 reduces the number of NMJ boutons in cpxSH1 mutants even further, below the control levels and is comparable to that observed in witA12/witB11 mutants alone.

    One copy of witA12 suppresses the increase in total bouton number seen in S6KL140 mutants.

    witA12/witB11 Acsl05847/AcslKO double mutants show a significant reduction in bouton number at neuromuscular junction 4, similar to witA12/witB11 mutants.

    witA12/+ significantly suppresses synaptic overgrowth of Acsl05847/AcslKO mutants.

    witA12/+ suppresses the increase in bouton number and satellite bouton number seen at the neuromuscular junction in spartin1/Df(3R)110 third instar larvae.

    witA12 spartin1/witB11 Df(3R)110 double mutant larvae show a significant decrease in bouton number and satellite bouton number at the neuromuscular junction compared to controls, as occurs in witA12/witB11 single mutant larvae.

    witA12/+ strongly suppresses the brain vacuolisation seen in 20 day old spartin1/Df(3R)110 adults.

    The neuromuscular junction overgrowth phenotype (increased total number of boutons and increased number of satellite boutons) of brat11/brat2L-192-9 larvae is not suppressed by witA12/+.

    Expression of twitScer\UAS.cKa under the control of Scer\GAL4elav.PU slightly, but significantly, enhances the reduction in synaptic terminal size at the neuromuscular junction seen in witB11/witA12 larvae.

    Expression of twitScer\UAS.cKa under the control of Scer\GAL4elav.PU has no effect on the size of the evoked excitatory junctional potential (EJP) at the neuromuscular junction in witB11/witA12 larvae.

    Expression of twitScer\UAS.cKa under the control of Scer\GAL4elav.PU has no effect on miniature EJP (mEJP) amplitude at the neuromuscular junction in witB11/witA12 larvae, while mEJP frequency is slightly increased.

    The neuromuscular junction expansion phenotype seen in cmpyΔ8 mutants is partially suppressed when animals are also heterozygous for witA12.

    witA12, cmpyΔ8 double mutants show a 44% reduction in bouton number at neuromuscular junction 4, thereby phenocopying the neuromuscular junction undergrowth displayed by wit single mutants.

    witA12/witB11 suppresses the increase in average bouton number at the neuromuscular junction which is seen in larvae expressing Snx163A.Scer\UAS.T:Avic\GFP under the control of Scer\GAL4elav-C155.

    Expression of witA12/witHA3 suppresses the larval neuromuscular junction overgrowth and bouton number phenotypes seen when Rac1Scer\UAS.T:Hsap\MYC is expressed in motor neurons under the control of Scer\GAL4BG380, instead producing a reduction in bouton number similar to the phenotype seen in witA12/witHA3 third instar larvae.

    Expression of witA12/witHA3 fails to suppress the larval neuromuscular junction overgrowth and bouton number phenotypes seen when Rac1V12.Scer\UAS is expressed in motor neurons under the control of Scer\GAL4BG380.

    witA12/witHA3 suppresses the increase in evoked excitatory junctional potential (EJPs) and quantal content seen when Rac1Scer\UAS.cLa is expressed in motor neurons under the control of Scer\GAL4BG380, with third instar larvae instead displaying the reduction in neurotransmitter release phenotype seen in witA12/witHA3 mutants.

    Expression of trioScer\UAS.cBa in motor neurons under the control of Scer\GAL4BG380 partially suppresses the reduced bouton number phenotype seen in witA12/witHA3 larval neuromuscular junctions.

    Ranbp1170/+; witA12/+ double heterozygous larvae exhibit significantly fewer boutons than either wild-type or each heterozygous allele alone.

    WASp1/Df(3R)3450 partially suppresses the small neuromuscular junction phenotype seen in witA12/witB11 mutants.

    RhoGAP92B1/+ witA12/+ double heterozygous third instar larvae show a significant decrease in bouton number/muscle area and satellite bouton number at the neuromuscular junction compared to wild type.

    Expression of Cip4NIG.15015R or WASpGD1559 post-synaptically (under the control of Scer\GAL4C57) in witA12/witB11 larvae does not affect overall bouton number or satellite bouton formation.

    A witA12 heterozygous background can completely reverse the increase in total bouton number and satellite bouton formation in larvae expressing either Cip4NIG.15015R or WASpGD1559 post-synaptically (under the control of Scer\GAL4C57).

    Post-synaptic expression of DysdsRNA.mub.Scer\UAS under the control of Scer\GAL4eve.RN2 in a witA12/witB11 background increases the synaptic current as in a wild-type background.

    witA12/+ suppresses the increase in total bouton number at the neuromuscular junction that is seen in nwk1/nwk2 larvae.

    The increase in total bouton number at the neuromuscular junction that is seen in Dap160Δ1 larvae is suppressed by witA12/+.

    A witA12/witB11 transheterozygous background suppresses the synaptic overgrowth and increased bouton number phenotypes found in nwk1 homozygous third instar larvae, instead the larvae exhibit reduced synaptic growth and fewer boutons than wild type controls.

    spictmut neuromuscular junction overgrowth phenotypes are fully suppressed in witA12/witB11 mutants. The synaptic undergrowth phenotypes in larvae homozygous for spictmut in a witA12/witB11 background are indistinguishable from that of witA12/witB11 mutants alone. In addition, a heterozygous witA12 background partially suppresses the neuromuscular junction expansion of spictmut larvae.

    Expression of DysdsRNA.NH2.Scer\UAS postsynaptically (under the control of Scer\GAL4G14) in witA12/witB11 trans-heterozygous neuromuscular junctions results in similar EJP amplitudes and quantal content as in witA12/witB11 mutants.

    At 25oC ~80% of witA12/witB11, FmrfScer\UAS.cMa (driven by Scer\GAL4dimm-929) animals can partially escape the pupal case. At 28oC about 30% of females fully eclose, and some inflate their wings. While these animals move fairly well they usually die within several days without producing progeny. No rescue is seen in the size of the synapse. Nor is the primary defect in synaptic transmission rescued.

    One copy of witA12 suppresses the increased bouton number seen at the neuromuscular junction in spin10403/spink09905 animals. spin10403/spink09905 animals which are also mutant for witA12/witB11 show a further decrease in bouton number.

    Xenogenetic Interactions
    Statement
    Reference

    Heterozygosity for witA12 does not modify the fully penetrant rough eye phenotype resulting from the co-expression of HPV18\E6Scer\UAS.T:Hsap\MYC and Hsap\UBE3AScer\UAS.cRa under the control of Scer\GAL4GMR.PU, leading to severe eye necrosis.

    Complementation and Rescue Data
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    Stocks (2)
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    External Crossreferences and Linkouts ( 0 )
    Synonyms and Secondary IDs (5)
    References (55)