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General Information
Symbol
Dmel\Fmr1Δ50M
Species
D. melanogaster
Name
FlyBase ID
FBal0131033
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
dfmr150M, dfmr1Δ50M, Fmr1Δ50, dFmr1Δ50, dxfr150M
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
Deletion removing P{EP} and flanking DNA including the 5' non coding exons and the first coding exon of the Fmr1 gene.
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 )
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
dorsal cluster neuron & neurite (with Fmr1Δ113M)
gamma-lobe & neuron | somatic clone
mushroom body & neuron & dendrite | somatic clone
mushroom body & neuron | somatic clone
photoreceptor cell & synapse & lamina receptor cell
Detailed Description
Statement
Reference
Bouton numbers are unaffected at the NMJ of Fmr1Δ50M/+ third instar larvae.
Fmr1Δ50M adult heterozygotes do not display any overt eye morphology defects but display memory defects in an aversive olfactory conditioning assay (their olfactory perception however is not disrupted). Fmr1Δ50M homozygous adults exhibit mushroom body defects including missing or thinned mushroom body α-lobes and β-lobe fusion.
Fmr1Δ50M/Fmr1Δ50M larvae show significant increases in the number of type I boutons at the neuromuscular junction, compared to controls.
Fmr1Δ50M/Df(3R)Exel6265 and Fmr1Δ50M/Fmr13 mutant females display a strong reduction in fertility. Ovaries of Fmr1Δ50M/Df(3R)Exel6265 mutants, and a subset of Fmr1Δ50M/Fmr13 mutants, display developmental defects, including fused egg chambers, aberrant nurse cell numbers, disorganized germaria often fused to an egg chamber, and occasional oocyte misspecification or multiple oocytes per egg chamber.
Fmr1Δ50M homozygotes are viable, male sterile and female semi-fertile. Fmr1Δ50M heterozygous males and females are semi-fertile. Fmr1Δ50M/Fmr1Δ113M transheterozygotes are male sterile and female semi-fertile. Fmr1Δ50M homozygosity and Fmr1Δ50M/Fmr1Δ113M transheterozygosity lead to the formation of crystalline aggregates (of Stellate protein) in spermatocytes, which are absent in Fmr1Δ50M heterozygotes and wild-type controls.
Fmr1Δ50M/Fmr1Δ50M, but not Fmr1Δ50M/+, mutants display a striking expansion of dendritic arbors in MVP2 neurons at day 1 post-eclosion, as compared to controls, with a significant increase in total dendritic arbor volume; the central core of arbors is much wider than that of wild type, with less-pronounced anterior and posterior ends; homozygous mutant arbors occupy a greater dorsoventral depth as compared with wild type. Projection neuron dendritic arbors in Fmr1Δ50M/Fmr1Δ50M mutants also exhibit overgrowth, with a significant increase in total dendritic arbor volume, as compared to controls. These dendritic arbor expansion phenotypes are not observed at earlier developmental time points, measured at pupal day 4, and 1 hour post-eclosion.
The presynaptic terminal length of class IV dendritic arborizing neurons in Fmr1Δ50M/Fmr1Δ50M MARCM somatic clones in third instar larvae is significantly increased compared to controls.
Fmr1Δ50M/Fmr1Δ50M flies do not exhibit any significant difference in the number, distribution or density of GABAergic neurons, or the GABAergic mushroom body calyx innervation, but do show frequent mushroom body beta lobe crossing and fusion at the midline, and absence or loss of mushroom body lobes, most often the alpha lobe, as compared to controls. Fmr1Δ50M/Fmr1Δ50M flies exhibit a strong learning deficit in an associative learning assay. Fmr1Δ50M/Fmr1Δ50M GABAergic neuron clones do not show any significant difference in cumulative process length, as compared to control clones, but do exhibit a differential developmental trajectory in process elaboration, with a highly significant increase in process length between days 1 and 5 post-eclosion, and they also show altered depolarization-induced calcium signaling dynamics, in comparison to control neurons. Fmr1Δ50M/Fmr1Δ50M GABAergic neuron clones with only a primary process show a significant increase in total length at 5 days post-eclosion, and those with 5 or more processes show a significant decrease in total process length at 1 day post-eclosion, as compared to control neurons. Fmr1Δ50M/Fmr1Δ50M GABAergic neuron clones with 2-4 processes do not exhibit any significant difference in total process length as compared to controls. Fmr1Δ50M/Fmr1Δ50M GABAergic neuron clones with 5 or more processes show significantly shorter primary and secondary processes and fewer secondary and tertiary branches at 1 day post eclosion, as compared to controls, but these differences are not seen at 5 days post-eclosion.
Homozygotes are viable and do not display obvious growth phenotypes. Fmr1Δ50M mutant eyes, generated by eyFLP/FRT-mediated mitotic recombination, do not show an increase in ommatidial number.
Neuromuscular junctions in Fmr1Δ50M/Fmr1Δ50M mutant larvae exhibit significantly increased branch number and increased type I synaptic bouton number, and significantly increased amplitude of evoked junctional currents, as compared to controls.
A Fmr1Δ50M mutant C4 ddaC neuron clones causes mild but significant overgrowth of presynaptic terminals.
Homozygous third instar larvae show an increase in bouton number and satellite bouton number at the neuromuscular junction compared to controls.
Fmr1Δ50M mutant third instar larvae exhibit neuromuscular junction abnormalities in muscle 4. Their synaptic branch and bouton numbers are significantly higher than in wild type flies.
Mutant males and females show an increase in daytime sleep intensity compared to controls.
The Fmr1Δ50M mutant brain is unaltered in size and gross architecture compared with controls. However synaptogenesis defects can be seen including elevated synaptic area, increased synaptic branching and the formation of supernumerary synaptic boutons. Developmentally arrested satellite boutons also accumulate in Fmr1Δ50M mutant larvae. Futsch positive loops accumulate in Fmr1Δ50M mutant synaptic arbors. The brains of adult Fmr1Δ50M mutants exhibit strikingly abnormal small ventrolateral (sLN[[v]] neuron synaptic architecture with expanded terminals containing supernumerary synaptic boutons. Fmr1Δ50M mutant flies have approximately 70 Pdf positive boutons in the dorsal horn and protocerebrum compared to around 40 in controls. Fmr1Δ50M mutants display a highly significant decrease in olfactory learning compared to controls.
A particularly prominent defect in Pdf neurons not reported previously is the aberrant appearance of a class of Pdf neurons in the central brain of Fmr1Δ50M mutants. This class of neurons is a developmentally-transient population of triocerebral Pdf neurons. These neurons are not observe in age-matched adult wild-type brains. In mutants, these neurons are often present at a bilaterally oriented pair with cell body positioning in the tritocerebrum, near the esophageal foramen. Mutant Pdf neurons project their axons upward beyond the posterior optic tract and elaborate a synaptic field in the protocerebral area adjacent to the sLN[[v]] synaptic arbors. Thus, in addition to connectivity defects within the s- and lLN[[v]] neurons, the PDF circuit may be compromised by the encroaching aberrant contributions of the midline PDF tritocerebral (PDF-TRI) neurons present only in Fmr1Δ50M mutants. Upon eclosion, wild-type and mutant brains show an indistinguishable array of PDF-TRI neurons. However, in the proceeding days, these cells are rapidly lost in control brains, while retained in Fmr1Δ50M mutants. The inappropriately retained Fmr1Δ50M mutant PDF-TRI neurons maintain synaptic connectivity at maturity as well as depolarization-dependent Ca[2+] transients. No evidence of increased proliferation for the abnormally retained neurons is found, but rather clear indication of impaired apoptosis in Fmr1Δ50M mutant brains. Examination of crustacean cardioactive peptide (CCAP) and bursicon circuits, which are developmentally-transient and normally eliminated immediately post-eclosion in wild-type, reveal significantly delayed clearance compared with wild-type, however, the CCAP/bursicon neurons are also subsequently eliminated in Fmr1Δ50M mutants.
The number of NMJ branches (defined as a process with two or more boutons), is significantly higher in Fmr1Δ50M mutant third instar larvae compared to controls. The number of mature type 1b boutons is significantly increased in the Fmr1Δ50M null synapse and the number of immature satellite boutons is similarly elevated. The increase in number of mature boutons and the accumulation of satellite neurons are both rescued when the larvae are fed >20uM minocycline. The increase in NMJ arbor branch number is not restored upon treatment with minocycline. Small ventrolateral (sLN[[v]]) clock neurons in Fmr1Δ50M brains at three days post eclosion have an increased number and density of synaptic boutons, with overextension of their spatial distribution extending from the dorsal horn bifurcation point. These phenotypes are completely rescued upon feeding with minocycline. However, minocycline-treated Fmr1Δ50M null sLN[[v]] neurons continue to display a somewhat dispersed bouton array. In young adult brains (0-4 hours post-eclosion), single cell Fmr1Δ50M mutant MARCM clones in the adult mushroom body γ lobe show increased axonal length and excess synaptic branching compared to controls. Both of these defects are rescued upon treatment with minocycline.
Compared to wild-type, brain size and gross architecture of homozygous Fmr1Δ50M mutants appear unaltered. Dorsal projections into the protocerebrum in Fmr1Δ50M mutants exhibit a highly significant increase in the number of s-LNv Pdf neuron boutons compared with controls. Fmr1Δ50M mutants display defects on many levels of neuromuscular junction synaptic architecture, including grossly elevated synaptic area, increased synaptic branching, and the formation of supernumerary synaptic boutons. Most strikingly, developmentally arrested mini (or satellite) boutons accumulate int the mutants. Fmr1Δ50M males are completely sterile producing no viable progeny. In Fmr1Δ50M mutant spermatids, the central pair of axoneme microtubules is routinely lost, whereas the outer ring microtubule doublets are often deranged.
There is an increase in the total number of branches and the total number of boutons at the neuromuscular junction in mutant larvae compared to controls.
Fmr1Δ50M/Fmr1Δ50M, Fmr1Δ50M/Fmr1Δ113M and Fmr1Δ50M/Df(3R)Exel6265 adults sleep significantly longer each day than wild-type controls. The length of time they sleep each day increases with age up to some peak (for Fmr1Δ50M homozygotes: at 12 days in males, 42 days in females). Increased sleep in these animals is predominantly the result of increased number of sleep episodes and reduced number of brief awakenings, rather than increased average duration of sleep episodes. The increase in daily sleep in these mutants is also seen when animals are kept in permanent darkness. Fmr1Δ50M/Fmr1EP3517 adults sleep significantly longer per day than wild-type, although the effect is more subtle than in Fmr1Δ50M homozygotes and is more pronounced in females than in males. The increase in daily sleep in these flies is increased further by keeping them in permanent darkness. Under alternating 12 hours light and 12 hours dark conditions, Fmr1Δ50M/Fmr1Δ50M mutants show a circadian cycle of sleep. However, this differs from wild-type in having more sleep under light conditions and in lacking a reduction in sleep in anticipation of the end of dark conditions. Also unlike wild-type, under conditions of total darkness, Fmr1Δ50M/Fmr1Δ50M adults show no circadian rhythm in locomotor activity or sleep. Unlike wild-type flies, Fmr1Δ50M homozygotes do not recover significant amounts of sleep the day after 24 hours of sleep deprivation. However, following sleep deprivation they show reduced activity in response to a stimulus that causes arousal in wild-type or non-sleep deprived Fmr1Δ50M homozygotes. Fmr1Δ50M homozygotes have a reduced lifespan, with a steady death rate almost from eclosion, rather than a lag with few deaths in the first 28 days as seen in wild-type.
Fmr13/Fmr1Δ50M ovaries contain aberrant egg chambers with both increased and decreased numbers of germ cells per chamber compared to the normal number of 16. Fmr13/Fmr1Δ50M mutant germaria contain significantly more mitotic cells than controls. None of the completely mutant egg chambers in Fmr1Δ50M mosaic ovaries surrounded by heterozygous follicle cells exhibit proliferation defects. They appear morphologically normal.
Fmr1Δ50M mutant sLN[[v]] synaptic arbors display an overgrowth and over-elaboration phenotype. Fmr1Δ50M mutants exhibit an increased number of synaptic boutons throughout the sLN[[v]] terminal, projecting at minimum a further 20υm toward the midline and with a greatly increased average number of boutons beyond 50υm, compared to wild-type. Moreover, the number of synaptic boutons in every concentric ring is significantly elevated in Fmr1Δ50M mutants throughout the arbor. Both the number and spatial distribution of boutons in the sLN[[v]] synaptic arbor is altered in the absence of Fmr1, with more boutons occupying a larger territory beyond the normal extent of the sLN[[v]] arborization. Overexpression of Fmr1Scer\UAS.cZa at the earliest stage of pupal development, under the control of RU486-induced Scer\GAL4elav.Switch.PO exacerbates the Fmr1Δ50M mutant phenotype resulting in an elevated number of Pdf-positive synaptic boutons redistributed within 30% of the sLN[[v]] axonal arbor. Similarly, induction at pupal stage P2 provides no significant influence upon the synaptic arborization, with no change in the total number of Pdf-positive boutons. Overexpression of Fmr1Scer\UAS.cZa in the latter stage of pupal development, under the control of RU486-induced Scer\GAL4elav.Switch.PO ameliorates the Fmr1Δ50M mutant phenotype, restricting the number and specificity of synaptic connections.
Fmr1Δ50M mutants do not display defects in coordinated behavior (such as in a roll-over assay). Fmr1Δ50M mutants display significant overbranching in the neuromuscular synapse. Treatment of these mutants with the mGluR antagonist MPEP, which blocks mGluR signaling, suppresses the Fmr1Δ50M overbranching phenotype. Fmr1Δ50M mutant synaptic terminals display a significant increase in total area, compared to controls. Fmr1Δ50M mutants treated with the mGluR antagonist MPEP, which blocks mGluR signaling, display a significantly decreased synaptic area compared to non-treated mutants. However, MPEP-treated control animals display a similar decrease compared to non-treated controls, leading to the difference between the MPEP-treated wild-type control and the MPEP-treated Fmr1Δ50M mutant remaining significant, indicating that blocking mGluR signaling does not significantly rescue the increased synaptic terminal area characteristic of Fmr1Δ50M mutants. Fmr1Δ50M mutants display a significant increase in the number of synaptic boutons in the neuromuscular junction. Treatment of these mutants with the mGluR antagonist MPEP, which blocks mGluR signaling, does not rescue this increased bouton defect. At the ultrastructural level, the overall appearance of a bouton and the postsynaptic subsynaptic reticulum in Fmr1Δ50M mutants appears normal. Quantitatively, there is no significant difference in bouton size, mitochondria size, active zone size/number or the postsynaptic subsynaptic reticulum between Fmr1Δ50M mutants and control larvae. Fmr1Δ50M mutants display significant increases of synaptic vesicle density throughout the synaptic bouton clustered vesicle number surrounding active zones and docked vesicle number at the T-bar membrane. overall, Fmr1Δ50M mutants display a significant ~30% increase in overall vesicle number. Fmr1Δ50M mutants display a significant ~50% increase in the pool of clustered vesicles around the active zone. Fmr1Δ50M mutants display a significant ~85% increase in the number of docked vesicles at the active zone. Fmr1Δ50M mutant mushroom body neurons display axonal overgrowth, with both the axon branch number and the total axon branch length significantly increased in these mutants compared to controls. Treatment of these MARCM clone animals with the mGluR antagonist MPEP can effectively rescue the axon overgrowth and increased branching defects in these mutants.
At prepupal stage 4, but not stage 3, Fmr1Δ50M homozygous gamma neuron clones in a Fmr1Δ50M heterozygous background show longer axons with the same number of., but larger, branches, as compared to controls. Mutant neurons show a normal increase in size before eclose but show delayed pruning at eclosion, as they exhibit a decrease in axon branching only at day 4 after eclosion instead of at eclosion. In 4 days old adults reared under sensory deprivation, Fmr1Δ50M homozygous gamma neuron clones (in a Fmr1Δ50M heterozygous background) display a more pronounced increase in axon branch number, a significant increase in axon branch length and a failure in pruning, as compared to controls.
In just under 10% of homozygous Fmr1Δ50M mutants, the β lobe of the mushroom body is misdirected or missing. Just under 20% of homozygous Fmr1Δ50M mutants display a misdirected or missing α-lobe. In just under 70%, both the α- and β lobes of the mushroom body are either misdirected or missing. Where the β-lobe is present, just under 10% display severe midline crossing (defined as a densely strained band equal to or greater in width and thickness than those of the adjacent β-lobes), with approximately 25% displaying moderate midline crossing (defined as when the thickness of the fiber bundle crossing the midline is considerable but less than the width of the β-lobe termini). Just under 10% display mild midline crossing phenotypes in the β lobe (defined as when a thin band of fibers cross the midline). Approximately 10% of Fmr1Δ50M/Fmr1Δ113M transheterozygotes display misdirecting or missing α lobes. Approximately just over 70% of transheterozygous Fmr1Δ50M/Fmr1Δ113M mutants exhibit severe midline crossing in the β-lobe of the mushroom body (defined as a densely strained band equal to or greater in width and thickness than those of the adjacent β-lobes). The rest appear phenotypically normal. No sexual dimorphism in penetrance or expressivity is found.
Mutant adults have normal gross brain morphology, including an architecturally normal mushroom body. Mild β lobe overgrowth is seen at a slightly higher frequency than wild type. Single cell mutant clones in the mushroom body (in a wild-type background) produce additional cell body processes compared to wild-type single cell clones (converting the characteristic unipolar mushroom body neurons seen in wild-type into multipolar neurons); there is a 3-fold increase in the number of cell body processes in the mutant cells. The mutant cells show a more complex and disordered dendritic structure compared to wild type; primary dendrites display clear secondary branches and the fine dendritic processes that are normally restricted to the termini spread aberrantly along the primary branches. Single cell mutant γ neurons in the mushroom body always have significantly increased axonal branching and significantly more and longer axonal branches than control cells. The large, extra branches do not follow the main axon trajectory, but instead extend in apparently random directions to invade inappropriate territory. Neurons in large mutant clones in the mushroom body show a significantly enlarged average bouton area and more variable distribution of bouton sizes than wild type. The mutant presynaptic boutons are almost filled with vesicles; the average area of the bouton occupied by vesicles is increased 50% in mutant boutons to nearly 75% of the bouton.
When mutant female are mated with wild-type males, only 21% of the expected progeny produced. Mutant males have enlarged testes. The diameter of the tip of the testis is similar to controls, but the diameter in the middle of the testis is about 50% larger than wild-type. This phenotype is 100% penetrant in newly enclosed flies, but it abates with aging. Other than this the morphology of mutant testes appears normal. The testis phenotype appears to be caused by the accumulation of misarranged spermatid bundles within the testis lumen. The coiled spermatid bundles normally seen at the testis base are missing in mutants. Instead of mature spermatids, degenerated cell debris fill the base of mutant testes. The early individualisation process of spermatogenesis does appear to progress largely as normal (occasional defects are seen). However, the orientation of spermatid tails within a cyst is often arranged in an irregular fashion in mutants. In addition the configuration of mitochondria and axoneme within a sperm flagellum is variably skewed, as well as some unknown ring structures present at the inner-space between spermatid tails which is not seen in controls. There is also a specific disruption of the microtubule axoneme structure in the sperm flagellum which becomes progressively more pronounced at spermatid differentiation proceeds. The central pair microtubules are missing in mutant axonemes, although the outer microtubules are still present. this phenotype is progressive, 30% of early stage spermatids, and 56% of late-stage spermatid.
Mutants show a fibre extension defect in the DC and LNv neurons. Extension of DC axons from the lobula to the medulla is incomplete, some axons show guidance errors. LNv neurons may over extend, show guidance defects or show aberrant morphology. The LVn defects are less consistent than those in the DC neurons. Stereotypical grid-like array of neurites entering the medulla is disrupted in mutant flies - short and thin branches fail to connect. This occurs even for neurons that do cross towards the distal medulla. Homozygotes show 0% eclosion from pupal case.
Mutants show no morphological defects. When tested for bang sensitivity, temperature sensitivity and phototaxis there is no detectable difference between wild type and mutant. However there are defects in coordination in a simple flight test. Synaptic transmission is reduced (as indicated by a reduction in off-transient mean amplitude as assayed by ERG). Null mutants show pronounced synaptic overgrowth and overelaboration of synaptic terminals. Muscle 4 has 51% increase in number of boutons over controls. Arboreal branching is increased - with muscle 4 showing 50% more branches than wild type. Evoked synaptic transmission at the NMJ is elevated. Mean EJC amplitude is increased. Average synaptic efficacy is upregulated.
External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement
Reference
Fmr1Δ50M has memory defective | adult stage phenotype, enhanceable by Nab2ex3/Nab2[+]
NOT Enhanced by
Statement
Reference
Suppressed by
Statement
Reference
Fmr1Δ50M/Fmr13 has cell number defective | adult stage phenotype, suppressible by Zfrp8[+]/Zfrp8SM206
Fmr1Δ50M/Fmr13 has female semi-sterile phenotype, suppressible | partially by Zfrp8[+]/Zfrp8SM206
Fmr1Δ50M/Fmr1Δ113M has sterile phenotype, suppressible by aubsting-1/aub[+]
Fmr1Δ50M has neuroanatomy defective phenotype, suppressible by CenG1A[+]/CenG1AEY01217
NOT suppressed by
Enhancer of
NOT Enhancer of
Suppressor of
Statement
Reference
NOT Suppressor of
Other
Phenotype Manifest In
Enhanced by
Statement
Reference
Fmr1Δ50M has terminal bouton phenotype, enhanceable by mGluR112b
NOT Enhanced by
Suppressed by
Statement
Reference
Fmr1Δ50M/Fmr13 has ovary | adult stage phenotype, suppressible by Zfrp8[+]/Zfrp8SM206
Fmr1Δ50M/Fmr13 has egg chamber | adult stage phenotype, suppressible by Zfrp8[+]/Zfrp8SM206
Fmr1Δ50M/Fmr13 has nurse cell | adult stage phenotype, suppressible by Zfrp8[+]/Zfrp8SM206
Fmr1Δ50M/Fmr13 has germarium | adult stage phenotype, suppressible by Zfrp8[+]/Zfrp8SM206
Fmr1Δ50M/Df(3R)Exel6265 has ovary | adult stage phenotype, suppressible by Zfrp8[+]/Zfrp8SM206
Fmr1Δ50M/Df(3R)Exel6265 has nurse cell | adult stage phenotype, suppressible by Zfrp8[+]/Zfrp8SM206
Fmr1Δ50M has spermatocyte | spermatogenesis phenotype, suppressible by aubsting-1/aub[+]
Fmr1Δ50M has synapse phenotype, suppressible by Dscam118
Fmr1Δ50M has NMJ bouton phenotype, suppressible by RanBPMk05201/l(2)k05201[+]
Fmr1Δ50M/Fmr13 has nurse cell phenotype, suppressible | partially by CblF165/Cbl[+]
Fmr1Δ50M has synaptic vesicle phenotype, suppressible by mGluR112b
Fmr1Δ50M has bouton phenotype, suppressible by futschN94
Fmr1Δ50M has synapse phenotype, suppressible by futschN94
NOT suppressed by
Statement
Reference
Fmr1Δ50M has mushroom body beta-lobe | adult stage phenotype, non-suppressible by Nab2ex3/Nab2[+]
Fmr1Δ50M/Fmr13 has nurse cell | supernumerary phenotype, non-suppressible by CblF165/Cbl[+]
Fmr1Δ50M has synapse phenotype, non-suppressible by mGluR112b
Fmr1Δ50M has presynaptic active zone phenotype, non-suppressible by mGluR112b
Enhancer of
Statement
Reference
NOT Enhancer of
Suppressor of
Statement
Reference
NOT Suppressor of
Other
Additional Comments
Genetic Interactions
Statement
Reference
The mushroom body α-lobe morphological defects characteristic for Fmr1Δ50M homozygous adults are ameliorated by combination with a single copy of Nab2ex3, whereas the reverse is true for Nab2ex3 homozygotes in which the combination with one copy of Fmr1Δ50M further worsens the α-lobe phenotype. The β-lobe fusion observed in either of the two homozygous mutants cannot be modified by heterozygosity of the other gene's allele. The mild memory defects displayed by the Fmr1Δ50M heterozygotes in an aversive olfactory conditioning assay are enhanced by Nab2ex3 heterozygosity. The eye defects (reduced size, partial depigmentation and disorganization of the ommatidial lattice) observed in adult flies expressing Nab2EP3716 under the control of Scer\GAL4GMR.PU can be suppressed by combination with a single copy of Fmr1Δ50M.
Expression of TorsindsRNA.Scer\UAS.WIZ driven by Scer\GAL4αTub84B.PL does not enhance increased numbers of type I NMJ boutons seen in Fmr1Δ50M/Fmr1Δ50M larvae.
Zfrp8SM206/+ partially restores fertility and suppresses the majority of ovary defects in Fmr1Δ50M/Df(3R)Exel6265 mutants, restoring cell division in the germline, normal oogenesis, and normal egg chamber morphology and separation, although the first egg chamber often still appears fused to the germarium. Zfrp8SM206/+ partially restores fertility and restores ovary morphology to normal in Fmr1Δ50M/Fmr13 mutants.
The male sterility of Fmr1Δ50M/Fmr1Δ113M transheterozygotes and the crystalline aggregates observed in the spermatocytes of Fmr1Δ50M homozygotes are suppressed by aubsting-1/+ heterozygosity.
Heterozygous CenG1AEY01217 increases the viability of flies homozygous for Fmr1Δ50M. Heterozygosity for CenG1AEY01217 suppresses the mushroom body phenotype of beta-lobe fusion and the impaired short-term memory defect in homozygous Fmr1Δ50M flies.
The increased presynaptic terminal length of class IV dendritic arborizing neurons in Fmr1Δ50M/Fmr1Δ50M MARCM somatic clones in third instar larvae is completely suppressed by combination with Abl1 in heterozygous state.
rinNP3248/rin2, Fmr1Δ113M/Fmr1Δ50M animals reach a late pupal stage - pupae are long and slender. rinNP5420/rin2, Fmr1Δ113M/Fmr1Δ50M animals develop into adult flies that die soon after eclosion - pupae are long and slender. rinT:Disc\RFP-mCherry rescues the slender pupae phenotype and lethality associated with rinNP3248/rin2, Fmr1Δ113M/Fmr1Δ50M animals. rinT:Disc\RFP-mCherry rescues the slender pupae phenotype and lethality associated with rinNP5420/rin2, Fmr1Δ113M/Fmr1Δ50M animals.
dlpA187/+, or both dlpA187/+ and Sdc23/+, suppresses the increase in NMJ branching and synaptic bouton number; and both Sdc23/+ and dlpA187/+ (but not dlpA187/+ alone) suppresses the increased amplitude of evoked junctional currents seen in Fmr1Δ50M/Fmr1Δ50M mutant larvae.
The mild overgrowth of presynaptic terminals in Fmr1Δ50M mutant C4 ddaC neuron clones is completely abolished by a Dscam118 mutant background.
Fmr1Δ50M spartin1 and Fmr1Δ50M Dadj1E4 double heterozygous third instar larvae show an increase in bouton number and satellite bouton number at the neuromuscular junction compared to controls.
The number of synaptic branches and boutons in muscle 4 neuromuscular junctions is significantly lower in Top3β26 Fmr1Δ50M double mutant third instar larvae than in either mutant alone.
Expression of TimpScer\UAS.cPa under the control of Scer\GAL4da.G32 suppresses the NMJ defects seen in Fmr1Δ50M mutant third instar larvae. The mutant over-branching and supernumerary bouton formation have been eliminated, and the accumulation of developmentally arrested satellite boutons is prevented. Flies expressing TimpScer\UAS.cPa under the control of Scer\GAL4da.G32 in a Fmr1Δ50M mutant background are robust, healthy and fully viable. Homozygous Fmr1Δ50M fully suppresses the tracheal defects seen when TimpScer\UAS.cPa is expressed under the control of Scer\GAL4da.G32. Homozygous Fmr1Δ50M fully suppresses the tracheal defects seen in Mmp1Q112stop mutant flies. Homozygous Mmp1Q112stop partially suppresses the NMJ defects seen in Fmr1Δ50M mutant third instar larvae. Synaptic bouton number is strongly rescued and increased number of synaptic branches is suppressed.
The increased number of branches and of boutons at the neuromuscular junction of Fmr1Δ50M larvae is significantly suppressed by RanBPMk05201/+.
CblF165 is a dominant suppressor of the germ cell proliferation defects in Fmr13/Fmr1Δ50M mutant ovaries. The fewer germ cell phenotype is largely suppressed by CblF165/+, while the supernumerary germ cell phenotype is not suppressed at all.
7.7% of ban12/Fmr1Δ50M transheterozygous adult females are fertile. Double heterozygous adult females of ban12/Fmr1Δ50M display a significant increase in the number of germaria with one or no germline stem cells, compared to controls, that progressively worsens from day 2 post-eclosion to day 12.
A Fmr1Δ50M mutant background suppresses the behavioral/movement impairment seen in mGluR112b mutant larva. In these double mutants the roll-over behavioral response is smooth and efficient, with a significantly shorter 'struggle' time compared to mGluR112b single mutants. Quantitatively, the double mutant shows comparable behavior to the wild-type control. Fmr1Δ50M;mGluR112b double mutants display some suppression of the Fmr1Δ50M single mutant synaptic overbranching phenotype but the level of overbranching is still significant compared to wild-type controls. Fmr1Δ50M;mGluR112b double mutants do not show any suppression of the increased neuromuscular junction synaptic area characteristic of Fmr1Δ50M single mutants. Fmr1Δ50M;mGluR112b double mutants display a synergistic increase in synaptic bouton number compared to Fmr1Δ50M single mutants. Fmr1Δ50M;mGluR112b double mutants show a significant rescue of the elevated vesicle density phenotype seen in Fmr1Δ50M single mutants. This includes the clustered vesicles around the active zone.
Xenogenetic Interactions
Statement
Reference
The depigmentation phenotype in the adult eye and the lengthened time it takes for larvae to roll over in a turning assay characteristic for animals expressing Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa under the control of Scer\GAL4GMR.PU or Scer\GAL4Toll-6-D42 respectively, are exacerbated further by combination with Fmr1Δ50M in heterozygous state. The depigmentation phenotype in the adult eye and the lengthened time it takes for larvae to roll over in a turning assay characteristic for animals expressing Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP under the control of Scer\GAL4GMR.PU or Scer\GAL4Toll-6-D42 respectively, are exacerbated further by combination with Fmr1Δ50M in heterozygous state.
Expression of Hsap\FMR1Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav.PU rescues the neuromuscular junction synapse architecture defects seen in Fmr1Δ50M mutant third instar larvae. The increase in Futsch-positive loops is also fully rescued. Expression of Hsap\FMR1S500D.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav.PU rescues the neuromuscular junction synapse architecture defects seen in Fmr1Δ50M mutant third instar larvae. The increase in Futsch-positive loops is also fully rescued. Expression of Hsap\FMR1S500A.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav.PU is unable to rescue the neuromuscular junction synapse architecture defects seen in Fmr1Δ50M mutant third instar larvae. The increase in Futsch-positive loops is also not rescued. Expressing Hsap\FMR1Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav.PU rescues the expanded terminals and supernumerary synaptic boutons seen in the small ventrolateral neurons of Fmr1Δ50M mutant adults. Expressing Hsap\FMR1S500D.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav.PU rescues the expanded terminals and supernumerary synaptic boutons seen in the small ventrolateral neurons of Fmr1Δ50M mutant adults. Expressing Hsap\FMR1S500A.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav.PU fails to rescue the expanded terminals and supernumerary synaptic boutons seen in the small ventrolateral neurons of Fmr1Δ50M mutant adults. Expression of Hsap\FMR1Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4ey-OK107 rescues the decreases in olfactory learning seen in Fmr1Δ50M mutants. Expression of Hsap\FMR1S500D.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4ey-OK107 rescues the decreases in olfactory learning seen in Fmr1Δ50M mutants. Expression of Hsap\FMR1S500A.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4ey-OK107 fails to rescue the decreases in olfactory learning seen in Fmr1Δ50M mutants.
Expression of Hsap\FMR1Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155 completely suppresses the synaptic overgrowth defects characterising Fmr1Δ50M mutants. Expression of Hsap\FXR1Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155 fails to suppress the synaptic overgrowth defects characterising Fmr1Δ50M mutants. Expression of Hsap\FXR2Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155 fails to suppress the synaptic overgrowth defects characterising Fmr1Δ50M mutants. Expression of Hsap\FMR1Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155 fully rescues both the enlarged neuromuscular junctional area and increased synaptic branching that characterise Fmr1Δ50M mutants. Expression of Hsap\FXR1Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155 fails to suppress the enlarged neuromuscular junctional area and increased synaptic branching that characterise Fmr1Δ50M mutants. Expression of Hsap\FXR2Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155 fails to suppress the enlarged neuromuscular junctional area and increased synaptic branching that characterise Fmr1Δ50M mutants. Pre-synaptic expression of Hsap\FMR1Scer\UAS.T:Hsap\MYC using Scer\GAL4elav-C155 completely restores bouton number to control levels in Fmr1Δ50M mutants. Pre-synaptic expression of Hsap\FXR1Scer\UAS.T:Hsap\MYC using Scer\GAL4elav-C155 is totally incapable of restoring bouton number to control levels in Fmr1Δ50M mutants. Pre-synaptic expression of Hsap\FXR2Scer\UAS.T:Hsap\MYC using Scer\GAL4elav-C155 is totally incapable of restoring bouton number to control levels in Fmr1Δ50M mutants. Scer\GAL4elav-C155>Hsap\FMR1Scer\UAS.T:Hsap\MYC can strongly rescue the mini-bouton number in Fmr1Δ50M mutants back to wild-type levels. Scer\GAL4elav-C155>Hsap\FXR1Scer\UAS.T:Hsap\MYC is totally incapable of restoring the elevated mini-bouton number in Fmr1Δ50M mutants. Scer\GAL4elav-C155>Hsap\FXR2Scer\UAS.T:Hsap\MYC is totally incapable of restoring the elevated mini-bouton number in Fmr1Δ50M mutants. Expression of Hsap\FMR1Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4nos.UTR.T:Hsim\VP16 completely suppresses the male fecundity phenotype that characterises Fmr1Δ50M mutants. Expression of Hsap\FXR1Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4nos.UTR.T:Hsim\VP16 completely suppresses the male fecundity phenotype that characterises Fmr1Δ50M mutants. Expression of Hsap\FXR2Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4nos.UTR.T:Hsim\VP16 completely suppresses the male fecundity phenotype that characterises Fmr1Δ50M mutants. Expression of Hsap\FMR1Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4nos.UTR.T:Hsim\VP16 can fully restore the spermatid axoneme architecture in Fmr1Δ50M mutants. Expression of Hsap\FXR1Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4nos.UTR.T:Hsim\VP16 can fully restore the spermatid axoneme architecture in Fmr1Δ50M mutants. Expression of Hsap\FXR2Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4nos.UTR.T:Hsim\VP16 can fully restore the spermatid axoneme architecture in Fmr1Δ50M mutants.
The rough eye phenotype caused by expression of Hsap\MAPTV337M.Scer\UAS under the control of Scer\GAL4GMR.PF is not modified if the flies are also carrying Fmr1Δ50M.
Complementation and Rescue Data
Comments
The expression of Fmr1Scer\UAS.cZa under the control of Scer\GAL4T76 partially rescues the male sterility of Fmr1Δ50M homozygotes and of Fmr1Δ50M/Fmr1Δ113M transheterozygotes, and partially rescues the decreased fertilities of Fmr1Δ50M heterozygous males, of Fmr1Δ50M homozygous and heterozygous females, and of Fmr1Δ50M/Fmr1Δ113M transheterozygous females.
Expression of Fmr1Scer\UAS.cZa under the control of Scer\GAL4GMR12G04 (either in combination with a Gal80[ts] transgene to restrict expression to the period including pupal day 4 to 1 day post-eclosion, or without a Gal80[ts] for expression throughout development) significantly rescues the MVP2 dendritic arbor overgrowth seen in Fmr1Δ50M/Fmr1Δ50M mutants. Expression of Fmr1Scer\UAS.cZa under the control of Scer\GAL4GMR65G01 (either in combination with a Gal80[ts] transgene to restrict expression to the period including pupal day 4 to 1 day post-eclosion, or without a Gal80[ts] for expression throughout development) significantly rescues the projection neuron dendritic arbor overgrowth seen in Fmr1Δ50M/Fmr1Δ50M mutants.
Expression of Fmr1+t14 strongly diminishes PDF-TRI neuron retention in Fmr1Δ50M mutants.
Expression of Fmr1Scer\UAS.T:Hsap\MYC,T:Ivir\HA1 under the control of Scer\GAL4elav-C155 completely rescued the synaptic overgrowth characterising the Fmr1Δ50M mutant, and the terminals become clearly more restricted in extent and refined in the number of synaptic boutons. Expression of Fmr1Scer\UAS.T:Hsap\MYC,T:Ivir\HA1 under the control of Scer\GAL4elav-C155 fully rescues both the enlarged neuromuscular junctional area and increased synaptic branching that characterise Fmr1Δ50M mutants. Pre-synaptic expression of Fmr1Scer\UAS.T:Hsap\MYC,T:Ivir\HA1 using Scer\GAL4elav-C155 completely rescues bouton number back to control levels in Fmr1Δ50M mutants. Scer\GAL4elav-C155>Fmr1Scer\UAS.T:Hsap\MYC,T:Ivir\HA1 can strongly rescue the mini-bouton number in Fmr1Δ50M mutants back to wild-type levels. Expression of Fmr1Scer\UAS.T:Hsap\MYC,T:Ivir\HA1 under the control of Scer\GAL4nos.UTR.T:Hsim\VP16 completely rescues the male fecundity defect that characterises Fmr1Δ50M mutants. Expression of Fmr1Scer\UAS.T:Hsap\MYC,T:Ivir\HA1 under the control of Scer\GAL4nos.UTR.T:Hsim\VP16 can strongly rescue the spermatid axoneme defects that characterise Fmr1Δ50M mutants.
Provision of Fmr1 transiently during the early stages of neural development, through expression of Fmr1Scer\UAS.cZa under the RU486-induced control of Scer\GAL4elav.Switch.PO in a Fmr1Δ50M mutant background is not sufficient to correct the characteristic synaptic defects caused by the loss of Fmr1 as assayed at maturity. Provision of Fmr1 at maturity, following completion of neural development, is not sufficient to rescue the synaptic defects found in Fmr1Δ50M mutants.
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