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General Information
Symbol
Dmel\Mad12
Species
D. melanogaster
Name
FlyBase ID
FBal0044916
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
point mutation
Nucleotide change:
C3147538T
Reported nucleotide change:
C1601T
Amino acid change:
Q417term | Mad-PA; Q487term | Mad-PB
Reported amino acid change:
Q417term
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Cytology
Nature of the lesion
Statement
Reference
Amino acid replacement: Q417term.
Nucleotide substitution: C1601T.
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
ameliorates  Angelman syndrome
DOES NOT ameliorate  cardiomyopathy
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 
Mad12 suppresses muscle dysfunction but not the heart tube dysfunction of muscular dystrophy in Scgδ840 flies.
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference
Mad12/+ adults do not have any obvious wing phenotypes.
Mad12/Madk00237 transheterozygotes show a significant reduction in the number of synaptic boutons at the third instar larval neuromuscular junction, as compared to controls.
Mad12/+ third instar larvae have similar numbers of boutons to wild type.
Mad12 mutant nuclei are small and tightly packed, unlike wild-type copper cell nuclei, which are polyploid and regularly spaced. Eight days after induction of intestinal stem cell (ISC) clones, the number of cells in Mad12 mutant clones is significantly higher than in wild-type clones. After injury by feeding bleomycin, mutant clones have more cells than both wild-type clones and mutant clones before injury. Wild-type clones contain one stem cell, whereas approximately one-third of Mad12 mutant clones show a gradual increase in ISC number over time. One-stem-cell Mad12 mutant clones contain more stem cells than wild-type clones, indicating that mutant ISCs divide more often than wild-type ones.
Heterozygotes climb sightly, but significantly, better than wild-type controls in a negative geotaxis assay.
Very few Mad12 mutant wing disc clones are recovered.
Mad12/Mad7 mutant third instar larvae show increased uptake and transport of ingested fluorescently labeled fatty acids from the midgut lumen to the fat body compared to wild-type controls.
Clones of Mad12-mutant cells cause premature differentiation of the adult midgut precursor cells into large, polyploid, enterocyte-like cells compared with wild-type cells.
Somatic clones of Mad12 homozygous cells in the developing retina at 42 hours APF have abnormal arrangements of inter-ommatidial cells including aberrant bristle-bristle contacts and abberant arrangements of secondary and tertiary pigment cells.
Homozygous cells in the morphogenetic furrow (in clones that encompass the morphogenetic furrow) can stil achieve proper apicobasal contraction.
Mad12 mutant germline stem cells (GSCs) show maintenance and cell division defects when clones are generated during adult stages. However no defects are seen when Mad12 clones are generated during the larval and pupal stages.
Mosaic female germaria containing germline stem cells in contact only with homozygous somatic cap cells do not show any defects in germline stem cell renewal.
G1 arrest is delayed in Mad12 eye disc cells; some mutant cells don't arrest at all in larger Mad12 clones.
Homozygous clones in the wing disc extrude from the wing epithelium.
When neutral marked clones are induced in the ovary, the proportion of germaria carrying marked somatic stem cells 3 weeks after clone induction is around 70% of that seen one week after clone induction. For Mad12 homozygous clones, the equivalent figure is under 25%, resulting in significantly fewer clones in the follicle cells.
Mad11/Mad12 transheterozygotes exhibit abnormal L4/L5 wing veins, with no L2 or crossveins and a large margin notch.
Clones of male Mad12 homozygous germline stem cells are still present in less than 1% of testes one week after clone induction and none are present two weeks after clone induction. This is in contrast to wild-type control clones, which are present in 82% of testes one week after clone induction and 64% two weeks after clone induction.
The evoked excitatory junctional potential (EJP) (measured at muscle 6 of segment A3) shows a decrease in amplitude in Mad1/Mad12 animals compared to wild type. Quantal content is reduced compared to wild type.
The average number of crystal cells per embryo is significantly reduced in homozygous stage 13-14 embryos compared to wild type.
Ovarioles carrying Mad12 GSC clones are not recovered, but ovarioles with mutant Mad12 germ cells in egg chambers are recovered, indicating that Mad12 GSCs can not be maintained before adulthood.
Homozygous clones induced before 72 hours after egg laying (AEL) show elimination of entire tarsal segments, whereas if clones are induced after 84 hours AEL, only dorsal leg pattern features are affected.
In somatic clones induced late in the third larval instar L3 bifurcates or terminates at the clone boundary. L2 was seen to loop round a small clone. In 50 clones, all were seen to disrupt vein formation in a cell autonomous manner.
When somatic clones are created in the glial cells of the developing eye, they contain fewer cells than equivalent wild-type clones. the total number glial cells remains the same as wild-type cells appear to compensate for the loss of mutant ones.
Encapsulation defects of 16-cell cysts are seen in ovaries containing homozygous follicle cell clones.
Clones induced in the pleura showed a sternite or tergite identity rarely - 6 cases out of several hundred clones. Other clones retain a pleural identity or display a weak phenotype such as mild sclerotinization. Clones at or near the dorsal midline show loss of tergal pigmentation. A partial loss of pigmentation is often observed in clones lateral to the anterior inflection of the pigment band.
20% of the dorsal branch fusion events are disrupted. The fusion cell extends a sprout but does not contact the appropriate fusion partner.
Gastric caecae frequently fail to elongate. Dorsal trunk and visceral branches of the developing trachea are essentially normal. Branching defects occur, ganglionic branches fail to fuse. Dorsal trunk is normal.
Embryos lacking maternal and zygotic Mad function (Mad10/Mad12 embryos derived from females with homozygous Mad12 germ line clones) show loss of dorsal tissue and expansion of the lateral denticle bands into dorsal regions. The phenotype is partially paternally rescuable.
MadEz/Mad12 flies have imaginal disc defects. All the progeny of MadEz/Mad12 females mated to wild-type males die as embryos. One-half of the embryos (presumptive genotype Mad12/+ have a weakly ventralised phenotype, and the other half (presumptive genotype MadEz/+) have a variably expressive dorsal-open phenotype.
Females with homozygous germ line clones lay very few eggs, all of which are unfertilised and smaller than normal. The ovaries of these females may contain no discernible ovarioles or may contain many degenerating egg chambers, the most mature of which are at stage 10.
Clonal analysis in the germarium reveals that mutant stem cells are lost more rapidly than wild type, though there is no effect on the formation of 16 cell cysts or their subsequent development. Stem cell half life is 0.25 weeks (wild type being 4.6 weeks). Stem cell division rate relative to control is 0.21. Cysts contain the normal 16 cells, including and oocyte.
Clonal analysis revealed that Mad function is autonomously required in the eye imaginal disc cells for proliferation and/or survival.
Heterozygotes with Df(2L)C28 die as prepupae.
Larval heterozygotes with Df(2L)JS17 exhibit reduced fat body, midgut defects and greatly reduced gastric caecae and dissected pupae exhibit absent or severely reduced imaginal discs.
External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
NOT Enhanced by
Statement
Reference
Mad12 has lethal | recessive phenotype, non-enhanceable by lilliunspecified
Suppressed by
Enhancer of
Statement
Reference
Suppressor of
Statement
Reference
Mad12/Mad[+] is a suppressor | partially of visible | adult stage phenotype of Scer\GAL4A9, anchorGD3613
Mad12/Mad[+] is a suppressor of visible phenotype of Scer\GAL4A9, gbbUAS.cKa
Mad12/Mad[+] is a suppressor of visible phenotype of Scer\GAL4A9, dppUAS.cHa
Mad12/Mad[+] is a suppressor of visible phenotype of tkvSC143
Mad12/Mad[+] is a suppressor of visible phenotype of Scer\GAL4en-e16E, saxQ263D.UAS.cDa
NOT Suppressor of
Statement
Reference
Other
Statement
Reference
Mad12/Mad[+], dpphr27 has lethal | dominant phenotype
Phenotype Manifest In
NOT Enhanced by
Suppressed by
Enhancer of
Statement
Reference
Mad12/Mad[+] is an enhancer of interommatidial cell | ectopic | pupal stage P7 phenotype of shgR69
Mad12 is an enhancer of phenotype of dppe87
Mad12 is an enhancer of phenotype of dpphr56
NOT Enhancer of
Statement
Reference
Suppressor of
Statement
Reference
Mad12/Mad[+] is a suppressor | partially of wing vein phenotype of Scer\GAL4A9, anchorGD3613
Mad12/Mad[+] is a suppressor | partially of wing phenotype of Scer\GAL4A9, anchorGD3613
Mad12/Mad[+] is a suppressor | partially of wing vein phenotype of DdG0269
Mad12/Mad[+] is a suppressor of wing vein phenotype of Scer\GAL4A9, gbbUAS.cKa
Mad12/Mad[+] is a suppressor of wing phenotype of Scer\GAL4A9, dppUAS.cHa
Mad12/Mad[+] is a suppressor of wing phenotype of tkvSC143
Mad12/Mad[+] is a suppressor of wing vein | ectopic phenotype of tkvSC143
Mad12/Mad[+] is a suppressor of wing phenotype of Scer\GAL4en-e16E, saxQ263D.UAS.cDa
Mad12/Mad[+] is a suppressor of wing phenotype of tkvTAJ3
NOT Suppressor of
Statement
Reference
Mad12/Mad[+] is a non-suppressor of adult heart phenotype of Scgδ840
Mad12 is a non-suppressor of eye phenotype of Scer\GAL4hs.2sev, Tak1UAS.cMa
Mad12 is a non-suppressor of phenotype of Src42ASu(Raf)1-1
Other
Additional Comments
Genetic Interactions
Statement
Reference
Addition of Mad12/+ to animals expressing anchorGD3613 under the control of Scer\GAL4A9 partially suppresses the thickened wing vein phenotype and suppresses the increased wing size phenotype, to the extent that it is decreased compared to flies with Scer\GAL4A9 driver alone.
The decreased number of synaptic boutons at the third instar larval neuromuscular of Mad12/Madk00237 transheterozygotes is not suppressed or enhanced by either Nrx-1273 or Nlg1Δ46 homozygosity.
Mad12/+ suppresses the increase in total boutons (and satellite boutons) at the neuromuscular junction in Ube3a35/Ube3a35 third instar larvae.
The progeny from Mad12/+ mothers and dpphr4/+ fathers present embryo ventralization in less than half of cases, and near lethality, as compared to controls; the progeny from Mad12/+ mothers and dpphr27/+ fathers, but not dpphr56/+ or dppe87/+ fathers, exhibit semi-lethality, as compared to controls.
The neuromuscular junction overgrowth phenotype (increased total number of boutons and increased number of satellite boutons) of brat11/brat2L-192-9 larvae is significantly suppressed by Mad12/+. The reduced uptake of FM1-43 dye seen at the neuromuscular junction in brat11/brat2L-192-9 larvae is significantly suppressed by Mad12/+.
The severe loss of climbing ability in a negative geotaxis assay which is seen in Scgδ840 mutants is suppressed if the flies are also carrying Mad12/+. The dilated heart tube seen in Scgδ840 adults (detected as increased end-systolic and end-diastolic diameters as measured by optical coherence tomography) is is not rescued if the flies are carrying Mad12/+.
The aberrant wing vein phenotype seen in DdG0269/Y animals is suppressed by Mad12/+.
A Mad12 mutant background partially suppresses the overgrowth seen when ykiS168A.Scer\UAS.T:SV5\V5 is expressed in wing disc clones under the control of Scer\GAL4Scer\FRT.Act5C. Suppression of growth is evident in the distal wing, but not in the proximal wing. A Mad12 mutant background suppresses the overgrowth seen when ykiS250A.Scer\UAS.T:SV5\V5 is expressed in wing disc clones under the control of Scer\GAL4Scer\FRT.Act5C, returning the number of cells to control levels.
Homozygous Mad12 clones expressing cbtScer\UAS.cRa under the control of Scer\GAL4Act.PU do not survive in the wing pouch.
Strong maternal effect lethality is observed when trans-heterozygous Mad12 sax1 females are crossed with wild-type males. Strong maternal effect lethality is observed when trans-heterozygous Mad12 sax2 females are crossed with wild-type males.
brkXH/brkXH, MadB1/Mad12 double mutant wing disc clones have normal apical-basal cell length.
Smn73Ao/Mad12 and Smnf01109/Mad12 double heterozygotes show a reduction in bouton number per muscle area at the third larval instar neuromuscular junction compared to wild type.
Mad12/+ partially suppresses the abberant arangement of inter-ommatidial cells seen in the pupal and adult retinas of In(1)rst3/Y animals. The retinas of shgR69/+ animals at 42 hours APF have only very occasional inter-ommatidial patterning defects (the occasional extra or misplaced cell). This phenotype is significantly enhanced in Mad12/shgR69 transheterozygotes.
Mad12 mutant germline stem cells lacking one copy of Dcr-1Q1147X show clear stem cell maintenance defects when clones are generated during late larval/early pupal stages. Dcr-1Q1147X mutant germline stem cells lacking one copy of Mad12 show clear stem cell maintenance defects when clones are generated during late larval/early pupal stages. Expressing DlScer\UAS.P\T.cJa under the control of Scer\GAL4nos.PG in Mad12 mutant GSCs during the larval/pupal stages results in an enlargement of the niche at 7 and 14 days after clone induction. No stem cell maintenance defects are observed. The number of Mad12 mutant GSCs in the enlarged niche increases from 7 days to 14 days.
Eye disc cells simultaneously mutant for Mad12, ci94 and Su(H)del47 continue proliferating instead of arresting in G1 ahead of the morphogenetic furrow. The same phenotype is seen in cells mutant for Mad12 and ci94 - the presence of Su(H)del47 has no autonomous effect on G1 arrest. G1 arrest is delayed in Mad12, Su(H)del47 eye disc cells.
brkXH MadB1/Mad12 clones generated along the A/P boundary of the wing imaginal disc, using the FLP/FRT technique, show no defects in segregation behaviour. As with wild-type clones, these mutant clones stay in the compartment (anterior or posterior) in which they have been generated.
The weight of adp60/Mad12 double heterozygous flies is not significantly different from that of control flies.
Has no effect on the eye phenotype produced by activated arm constructs. (either armS44Y.GMR or armS56F.GMR).
When Mad12, smo3 double mutant somatic clones are made in the developing eye, a small but significant reduction in the percentage of mutant cells is seen compared to Mad12 clones alone.
Does not suppress the ability of Src42ASu(phl)1-1 to suppress the lethality of phl1/Y flies.
Shows a dominant maternal effect interaction with dpp; when Mad12/+ females are crossed to dpphr27/+ males, all progeny carrying dpphr27 die. This lethality is rescued by MadUbi-p63E.T:Hsap\MYC also partly by MedUbi-p63E.PD.
Heterozygosity for Mad12 weakly suppresses the blistered wing phenotype of tkvTAJ3.
Xenogenetic Interactions
Statement
Reference
Complementation and Rescue Data
Images (0)
Mutant
Wild-type
Stocks (4)
Notes on Origin
Discoverer
Comments
Comments
Mad mutations can be placed in an allelic series based on relative severity of the maternal effect enhancement of weak dpp alleles: Mad1 < Mad7 < Mad12 < Mad10 < Mad5 < Mad3 < Mad2 < Mad11 < Mad6 < Mad4 < Mad8 < Mad9.
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (6)
References (87)