Allele Dmel\th⁵

General Information
Symbol	Dmel\th⁵	Species	D. melanogaster
Name		FlyBase ID	FBal0050595
Feature type	allele	Associated gene	Dmel\th
Also Known As	th5, Diap1⁵

Map ( GBrowse )
Allele class	loss of function allele
Mutagen
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Nature of the Allele
Allele class	loss of function allele (Wang et al., 1999, Lisi et al., 2000)
Mutagen
Mutations Mapped to the Genome

Type Location Additional Notes References point mutation 3L:16,032,270..16,032,271 comment=G to A nucleotide change at the second or third position of the Trp codon leads to a nonsense mutation. (exact site of mutation unspecified). Site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change. evidence=experimental pr_change=W273\|th-PB,W273\|th-PC,W273@\|th-PA reported_pr_change=W273@ (Lisi et al., 2000)
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference Amino acid replacement: W273@. This mutation is within the second BIR domain. (Goyal et al., 2000) Amino acid replacement: W273@. W273 falls near the middle of the second BIR domain. (Lisi et al., 2000)
Cytology
Phenotypic Data
Phenotypic Class
	cell death defective \| recessive (Wang et al., 1999) increased cell death (Quinn et al., 2003, Rodriguez et al., 2002) lethal \| embryonic stage (Wang et al., 1999) lethal \| recessive (Goyal et al., 2000, Lisi et al., 2000) viable (with th^21-2s) (Geisbrecht and Montell, 2004)
Phenotype Manifest In
	border follicle cell (with th^21-2s) (Geisbrecht and Montell, 2004) border follicle cell \| somatic clone (Geisbrecht and Montell, 2004) egg chamber (with th^21-2s) (Geisbrecht and Montell, 2004) embryo (Lisi et al., 2000) embryonic epidermis (Wang et al., 1999) follicle cell \| supernumerary (with th^21-2s) (Geisbrecht and Montell, 2004) nurse cell \| supernumerary (with th^21-2s) (Geisbrecht and Montell, 2004)
Detailed Description
	Statement Reference th[5]/+ flies show near normal eye phenotype. (Arya et al., 2010) 14% of th⁵/th^21-2s egg chambers have border follicle cell migration defects, 25% have extra follicle cells and 3% have more than 15 nurse cells. 3% of th⁵/th^21-2s egg chambers show polarity defects. Homozygous follicle cells clones result in border follicle cell migration defects. (Geisbrecht and Montell, 2004) th⁵ homozygotes progress normally through gastrulation but arrest at the beginning of germ band extension, and within 90 min thereafter, adopt a characteristic morphology reflecting catastrophic events associated with widespread and synchronous apoptosis and arrest at stage 7. (Rodriguez et al., 2002) Heterozygotes are phenotypically wild type. (Hawkins et al., 2000) Embryos show increased cell death as assessed by TUNEL staining. The onset of this apoptosis appears several hours after development arrests. (Lisi et al., 2000) Epidermis of embryos does not form a cuticle. Homozygotes and hemizygotes undergo normal cellularization and initial gastrulation. During germ band extension all morphogenetic movements cease, cells adopt a rounded morphology (suggesting disruption if intercellular adhesion) and the yolk cell fragments and moves to the surface of the embryo. Cephalic furrow regresses. Surface of cells contain blebs and vesicular fragments characteristic of dying cells. Embryos show a significant increase in TUNEL-positive cells, but no significant change in acridine orange staining. Double mutants with Df(3L)H99 show a phenotype indistinguishable from that of th⁵ mutants alone. (Wang et al., 1999)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressed by
Statement Reference grim^GMR.PC, th⁵/th[+] has increased cell death phenotype, suppressible by Ark^CD4 (Rodriguez et al., 2002) Hsap\ATXN3^{tr.Q78.Scer\UAS.T:Ivir\HA1}, Scer\GAL4^GMR.PU, th⁵/th[+] has visible phenotype, suppressible \| partially by Hsp60D^{dsRNA.Sym.Scer\UAS}/Hsp60D^{a.Sym.Scer\UAS}, Scer\GAL4^GMR.PU (Arya et al., 2010) th⁵ has increased cell death phenotype, suppressible by Ark^CD4 (Rodriguez et al., 2002) th⁵ has increased cell death phenotype, suppressible by Buffy^Scer\UAS.cQa/Scer\GAL4^GMR.PF/Scer\GAL4^GMR.PF (Quinn et al., 2003) W^GMR.PG/W^GMR.PG, th⁵/th[+] has increased cell death phenotype, suppressible by Ark^CD4 (Rodriguez et al., 2002)
NOT suppressed by
Statement Reference Scer\GAL4^GMR.PU, Zzzz\CAG^{127Q.Scer\UAS.T:Ivir\HA1}, th⁵/th[+] has visible phenotype, non-suppressible by Hsp60D^{dsRNA.Sym.Scer\UAS}/Hsp60D^{a.Sym.Scer\UAS}, Scer\GAL4^GMR.PU (Arya et al., 2010)
Enhancer of
Statement Reference th⁵/th[+] is an enhancer of visible phenotype of Hsap\ATXN3^{tr.Q78.Scer\UAS.T:Ivir\HA1}, Scer\GAL4^GMR.PU (Arya et al., 2010) th⁵/th[+] is an enhancer of visible phenotype of Nc^GMR.PH (Hawkins et al., 2000) th⁵/th[+] is an enhancer of visible phenotype of Scer\GAL4^GMR.PU, Zzzz\CAG^{127Q.Scer\UAS.T:Ivir\HA1} (Arya et al., 2010) th⁵ is an enhancer of cell death defective phenotype of grim^GMR.PC (Lisi et al., 2000) th⁵ is an enhancer of cell death defective phenotype of rpr^GMR.PW (Lisi et al., 2000) th⁵ is an enhancer of cell death defective phenotype of W^GMR.PG/W^GMR.PG (Lisi et al., 2000) th⁵ is an enhancer of increased cell death phenotype of shtd¹ (Tanaka-Matakatsu et al., 2007) th⁵ is an enhancer of lethal phenotype of Nc^{Scer\UAS.T:Avic\GFP-EGFP}, Scer\GAL4^GMR.PF/Scer\GAL4^GMR.PF (Quinn et al., 2000) th⁵ is an enhancer of visible phenotype of Nc^{Scer\UAS.T:Avic\GFP-EGFP}, Scer\GAL4^GMR.PF/Scer\GAL4^GMR.PF (Quinn et al., 2000)
Other
Statement Reference grim^GMR.PC, th⁵/th[+] has increased cell death phenotype (Rodriguez et al., 2002) grim^GMR.PC, th⁵ has increased cell death phenotype (Rodriguez et al., 2002) W^GMR.PG/W^GMR.PG, th⁵/th[+] has increased cell death phenotype (Rodriguez et al., 2002) W^GMR.PG/W^GMR.PG, th⁵ has increased cell death phenotype (Rodriguez et al., 2002)
Phenotype Manifest In
Suppressed by
Statement Reference Hsap\ATXN3^{tr.Q78.Scer\UAS.T:Ivir\HA1}, Scer\GAL4^GMR.PU, th⁵/th[+] has ommatidium phenotype, suppressible \| partially by Hsp60D^{dsRNA.Sym.Scer\UAS}/Hsp60D^{a.Sym.Scer\UAS}, Scer\GAL4^GMR.PU (Arya et al., 2010) th⁵ has phenotype, suppressible \| partially by Scer\GAL4^{mat.αTub67C.T:Hsim\VP16}/BacA\p35^Scer\UAS.cHa (Yoo et al., 2002)
NOT suppressed by
Statement Reference Scer\GAL4^GMR.PU, Zzzz\CAG^{127Q.Scer\UAS.T:Ivir\HA1}, th⁵/th[+] has ommatidium phenotype, non-suppressible by Hsp60D^{dsRNA.Sym.Scer\UAS}/Hsp60D^{a.Sym.Scer\UAS}, Scer\GAL4^GMR.PU (Arya et al., 2010)
Enhancer of
Statement Reference th⁵/th[+] is an enhancer of border follicle cell phenotype of chic⁰¹³²⁰/chic²²¹ (Geisbrecht and Montell, 2004) th⁵/th[+] is an enhancer of border follicle cell phenotype of chic⁰¹³²⁰/chic^k13321 (Geisbrecht and Montell, 2004) th⁵/th[+] is an enhancer of eye phenotype of Nc^GMR.PH (Hawkins et al., 2000) th⁵/th[+] is an enhancer of ommatidium phenotype of Hsap\ATXN3^{tr.Q78.Scer\UAS.T:Ivir\HA1}, Scer\GAL4^GMR.PU (Arya et al., 2010) th⁵/th[+] is an enhancer of ommatidium phenotype of Scer\GAL4^GMR.PU, Zzzz\CAG^{127Q.Scer\UAS.T:Ivir\HA1} (Arya et al., 2010) th⁵ is an enhancer of eye phenotype of grim^GMR.PC (Lisi et al., 2000) th⁵ is an enhancer of eye phenotype of Nc^{Scer\UAS.T:Avic\GFP-EGFP}, Scer\GAL4^GMR.PF/Scer\GAL4^GMR.PF (Quinn et al., 2000) th⁵ is an enhancer of eye phenotype of rpr^GMR.PH (Hay et al., 1995) th⁵ is an enhancer of eye phenotype of rpr^GMR.PW (Lisi et al., 2000) th⁵ is an enhancer of eye phenotype of Scer\GAL4^hs.2sev, mbl^C.Scer\UAS (Vicente-Crespo et al., 2008) th⁵ is an enhancer of eye phenotype of shtd¹ (Tanaka-Matakatsu et al., 2007) th⁵ is an enhancer of eye phenotype of W^GMR.PG/W^GMR.PG (Lisi et al., 2000, Hay et al., 1995) th⁵ is an enhancer of ommatidium phenotype of shtd¹ (Tanaka-Matakatsu et al., 2007) th⁵ is an enhancer of phenotype of rpr^GMR.PW (Goyal et al., 2000) th⁵ is an enhancer of phenotype of W^GMR.PG/W^GMR.PG (Goyal et al., 2000)
Suppressor of
Statement Reference th⁵/th[+] is a suppressor of pigment cell \| supernumerary phenotype of morgue^unspecified (Hays et al., 2002)
Additional Comments
Genetic Interactions
Statement Reference A th[5] mutant background enhances the moderately rough eye phenotype observed upon expression of mbl[C.Scer\UAS] under the control of Scer\GAL4[hs.2sev]. (Vicente-Crespo et al., 2008) 80% of chic⁰¹³²⁰/chic^k13321 ; th⁵/+ egg chambers have border follicle cell migration defects. 77% of chic⁰¹³²⁰/chic²²¹ ; th⁵/+ egg chambers have border follicle cell migration defects. (Geisbrecht and Montell, 2004) The addition of W^GMR.PG to th⁵ heterozygotes leads to an enhancement of cell killing. The subsequent addition of Ark^CD4/Ark^CD4 suppresses that enhancement. The developmental arrest phenotype is also suppressed, embryos developing through stage 10. In about 5% of cases although no cell death is seen, arrest at stage 7 is still seen. (Rodriguez et al., 2002) Homozygous th⁵ embryos that express BacA\p35^Scer\UAS.cHa under the control of Scer\GAL4^{mat.αTub67C.T:Hsim\VP16} undergo normal morphogenesis until stage 11, after which massive cell death resumes. (Yoo et al., 2002) Addition of this allele strongly enhances the phenotype seen in rpr^GMR.PW and W^GMR.PG flies. (Goyal et al., 2000) Flies expressing intermediate levels of Nc^GMR.PH and also heterozygous for th⁵ have small eyes. (Hawkins et al., 2000)
Xenogenetic Interactions
Statement Reference The Hsp60D[dsRNA.Sym.Scer\UAS]-mediated suppression of the eye degeneration phenotype caused by Hsap\MJD[tr.Q78.Scer\UAS.T:Ivir\HA1] overexpression via Scer\GAL4[GMR.PU] is not much affected by heterozygosity for th[5]. The enhancement of the eye degeneration resulting from the overexpression of Zzzz\CAG[127Q.Scer\UAS.T:Ivir\HA1] via Scer\GAL4[GMR.PU] in a th[5]/+ background is not suppressed when Hsp60D[dsRNA.Sym.Scer\UAS] is co-expressed. Heterozygosity for th[5] enhances the eye degeneration resulting from the overexpression of Hsap\MJD[tr.Q78.Scer\UAS.T:Ivir\HA1] via Scer\GAL4[GMR.PU]. Heterozygosity for th[5] enhances the eye degeneration resulting from the overexpression of Zzzz\CAG[127Q.Scer\UAS.T:Ivir\HA1] via Scer\GAL4[GMR.PU]. (Arya et al., 2010) Homozygous th⁵ embryos that express BacA\p35^Scer\UAS.cHa under the control of Scer\GAL4^{mat.αTub67C.T:Hsim\VP16} undergo normal morphogenesis until stage 11, after which massive cell death resumes. (Yoo et al., 2002)
Complementation & Rescue Data
Fails to complement	th⁸ (Rodriguez et al., 2002)
Comments
Stocks ( 0 )

Notes on Origin
Discoverer

Comments
	grim^GMR.PC-induced apoptosis is enhanced by th⁵ to a slightly greater extent than by a deletion of th suggesting that a single complete BIR may have slight dominant negative properties. (Lisi et al., 2000)
External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 5 )
Reported As
Symbol Synonym	Diap1⁵ (Rodriguez et al., 2002) diap1⁵ (Xu et al., 2006) diap1^th5 (Ryoo et al., 2004) th5 (Hay et al., 2004, Hays et al., 2002, Yoo et al., 2002) th⁵ (Tanaka-Matakatsu et al., 2007, Vicente-Crespo et al., 2008, Arya et al., 2010)
Name Synonym
Secondary FlyBase IDs

References ( 17 )
Research paper	Arya et al., 2010, Ann. Neurosci. 17(1): 8--17 Hsp60D - A novel modifier of polyglutamine-mediated neuro degeneration in Drosophila. [FBrf0211649] Vicente-Crespo et al., 2008, PLoS ONE 3(2): e1613 Drosophila muscleblind is involved in troponin T alternative splicing and apoptosis. [FBrf0210274] Tanaka-Matakatsu et al., 2007, Dev. Biol. 309(2): 222--235 Mutation of the Apcl homologue shattered disrupts normal eye development by disrupting G1 cell cycle arrest and progression through mitosis. [FBrf0201230] Xu et al., 2006, Cell Death Differ. 13(10): 1697--1706 The effector caspases drICE and dcp-1 have partially overlapping functions in the apoptotic pathway in Drosophila. [FBrf0193497] Geisbrecht and Montell, 2004, Cell 118(1): 111--125 A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration. [FBrf0179220] Ryoo et al., 2004, Dev. Cell 7(4): 491--501 Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways. [FBrf0180124] Quinn et al., 2003, EMBO J. 22(14): 3568--3579 Buffy, a Drosophila Bcl-2 protein, has anti-apoptotic and cell cycle inhibitory functions. [FBrf0160857] Hays et al., 2002, Nat. Cell Biol. 4(6): 425--431 Morgue mediates apoptosis in the Drosophila melanogaster retina by promoting degradation of DIAP1. [FBrf0149131] Rodriguez et al., 2002, EMBO J. 21(9): 2189--2197 Unrestrained caspase-dependent cell death caused by loss of Diap1 function requires the Drosophila Apaf-1 homolog, Dark. [FBrf0147000] Yoo et al., 2002, Nat. Cell Biol. 4(6): 416--424 Hid, Rpr and Grim negatively regulate DIAP1 levels through distinct mechanisms. [FBrf0149130] Goyal et al., 2000, EMBO J. 19(4): 589--597 Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function. [FBrf0125392] Hawkins et al., 2000, J. Biol. Chem. 275(35): 27084--27093 The Drosophila caspase DRONC cleaves following glutamate or aspartate and is regulated by DIAP1, HID, and GRIM. [FBrf0129853] Lisi et al., 2000, Genetics 154(2): 669--678 Diverse domains of THREAD/DIAP1 are required to inhibit apoptosis induced by REAPER and HID in Drosophila. [FBrf0125418] Quinn et al., 2000, J. Biol. Chem. 275(51): 40416--40424 An essential role for the caspase dronc in developmentally programmed cell death in Drosophila. [FBrf0132365] Wang et al., 1999, Cell 98(4): 453--463 The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID. [FBrf0111512] Hay et al., 1995, Cell 83(7): 1253--1262 Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death. [FBrf0085196]
Review	Hay et al., 2004, Nat. Rev. Genet. 5(12): 911--922 The genetics of cell death: approaches, insights and opportunities in Drosophila. [FBrf0179925]

Allele Dmel\th5

Allele Dmel\th⁵