Van Vranken JG, Bricker DK, Dephoure N, Gygi SP, Cox JE, Thummel CS, Rutter J. SDHAF4 Promotes Mitochondrial Succinate Dehydrogenase Activity and Prevents Neurodegeneration. Cell Metab. 2014 Jun 18. pii: S1550-4131(14)00220-4. PMID: 24954416.
From the abstract: "Succinate dehydrogenase (SDH) occupies a central place in cellular energy production, linking the tricarboxylic cycle with the electron transport chain. As a result, a subset of cancers and neuromuscular disorders result from mutations affecting any of the four SDH structural subunits or either of two known SDH assembly factors. Herein we characterize an evolutionarily conserved SDH assembly factor designated Sdh8/SDHAF4, using yeast, Drosophila, and mammalian cells. ... These studies provide insights into the mechanisms by which SDH is assembled and raise the possibility that some forms of neuromuscular disease may be associated with mutations that affect this SDH assembly factor."
Showing posts with label Enzyme Deficiency. Show all posts
Showing posts with label Enzyme Deficiency. Show all posts
Sunday, July 20, 2014
Saturday, May 10, 2014
Addressing metabolic issues in a fly model of Adenine Nuclear Translocase (ANT) insufficiency
Vartiainen S, Chen S, George J, Tuomela T, Luoto KR, O'Dell KM, Jacobs HT. Phenotypic rescue of a Drosophila model of mitochondrial ANT1 disease. Dis Model Mech. 2014 May 8. PMID: 24812436.
From the abstract: "... Our findings illustrate the potential of different therapeutic strategies for ANT-linked diseases, based on increasing mitochondrial bioenergy production, or on alleviating metabolic stress."
From the abstract: "... Our findings illustrate the potential of different therapeutic strategies for ANT-linked diseases, based on increasing mitochondrial bioenergy production, or on alleviating metabolic stress."
Tuesday, April 23, 2013
Classic Galactosemia (aka Type I Galactosemia) and long-term outcomes. Characterization of a fly model. Recent report.
Ryan EL, DuBoff B, Feany MB, Fridovich-Keil JL. Mediators of a long-term movement abnormality in a Drosophila melanogaster model of classic galactosemia. Dis Model Mech. 2012 Nov;5(6):796-803. doi: 10.1242/dmm.009050. PMID: 22736462; Now freely available at PMCID: PMC3484862.
From the abstract: "... our results confirm that, like human patients, GALT-null Drosophila experience significant long-term complications that occur independently of galactose exposure, and serve as a proof of principle demonstrating utility of the GALT-null Drosophila model as a tool for exploring genetic and environmental modifiers of long-term outcome in GALT deficiency."
See this post for comments from Annette Parks regarding galactosemia model fly stocks at BDSC.
From the abstract: "... our results confirm that, like human patients, GALT-null Drosophila experience significant long-term complications that occur independently of galactose exposure, and serve as a proof of principle demonstrating utility of the GALT-null Drosophila model as a tool for exploring genetic and environmental modifiers of long-term outcome in GALT deficiency."
See this post for comments from Annette Parks regarding galactosemia model fly stocks at BDSC.
Tuesday, September 4, 2012
Comparison of the glycobiology of humans and flies. Foundational review.
In this recent review, the authors provide a comparison of human and fly glycobiology and describe the "increasing opportunities to dissect pathologic mechanisms using Drosophila genetics."
Katoh T, Tiemeyer M. The N's and O's of Drosophila glycoprotein glycobiology. Glycoconj J. 2012 Aug 31. PubMed PMID: 22936173
The authors indicate that the proteins and pathways discussed are relevant to a number of diseases, including retinitis pigmentosa, Peters Plus syndrome, and diseases "such as autoimmunity, cancer progression, and congenital heart disease, in which altered mucin type O-glycosylation has been implicated."
Peters Plus syndrome is also known as Krause–van Schooneveld–Kivlin syndrome and Krause–Kivlin syndrome. It is listed on Orphanet and you can read more about it at GeneReviews.
If someone has the time and inclination to pull out the Drosophila gene names mentioned in the paper, and list them as a comment here, please do so.
Katoh T, Tiemeyer M. The N's and O's of Drosophila glycoprotein glycobiology. Glycoconj J. 2012 Aug 31. PubMed PMID: 22936173
The authors indicate that the proteins and pathways discussed are relevant to a number of diseases, including retinitis pigmentosa, Peters Plus syndrome, and diseases "such as autoimmunity, cancer progression, and congenital heart disease, in which altered mucin type O-glycosylation has been implicated."
Peters Plus syndrome is also known as Krause–van Schooneveld–Kivlin syndrome and Krause–Kivlin syndrome. It is listed on Orphanet and you can read more about it at GeneReviews.
If someone has the time and inclination to pull out the Drosophila gene names mentioned in the paper, and list them as a comment here, please do so.
Tuesday, August 28, 2012
Brain disease and fly models. Foundational review.
This review touches on a number of neurological and neuromuscular
degenerative diseases, metabolic disorders, tumors, epilepsy and trauma
(injury and regeneration).
Jeibmann & Paulus (2009) Drosophila melanogaster as a model organism of brain diseases. Int J Mol Sci. 2009 Feb;10(2):407-40. PubMed: 19333415; PubMed Central: PMC2660653.
Jeibmann & Paulus (2009) Drosophila melanogaster as a model organism of brain diseases. Int J Mol Sci. 2009 Feb;10(2):407-40. PubMed: 19333415; PubMed Central: PMC2660653.
Tuesday, August 21, 2012
Glycerol Kinase Deficiency Model. Recent Report.
Mutations in eye pigmentation genes were among the first identified in Drosophila and helped contribute to our understanding of general mechanisms of genetic inheritance. Now they're impacting our understanding of a human disease model. In the recent report cited below, the authors describe development of a fly model of glycerol kinase deficiency and subsequent analysis of the affected flies.
Open access paper.
New Fly Model: Glycerol kinase deficiency.
Wightman PJ, Jackson GR, Dipple KM. Glycerol hypersensitivity in a Drosophila model for glycerol kinase deficiency is affected by mutations in eye pigmentation genes. PLoS One. 2012;7(3):e31779. Epub 2012 Mar 9. PubMed PMID: 22427807; PubMed Central PMCID: PMC3302884.
The authors used RNAi knockdown and over-expression of Gyk and Dgk in the study, controlling expression of the RNAi reagent and ORFs with the Gal4-UAS system.
The authors indicate that mutations in the eye color genes brown, garnet, rosy, and vermillion, and the body color gene yellow modified glycerol hypersensitivity in the disease model flies.
Glycerol kinase deficiency is described at Wikipedia.
The relevant human genes at NCBI Gene include GK.
GK and the deficiency are described at OMIM.
Orphanet has some info on various forms of the deficiency.
Relevant fly genes include dGyk (Gyk in FlyBase) and dGK (Dgk in FlyBase).
Based on a DIOPT search, at least two other genes have significant similarity to GK, CG8298 and CG7995.
This review looks to be fairly comprehensive and includes comparison of DGKs in model species: Mérida I, Avila-Flores A, Merino E. Diacylglycerol kinases: at the hub of cell signalling. Biochem J. 2008 Jan 1;409(1):1-18. Review. PubMed PMID: 18062770
Open access paper.
New Fly Model: Glycerol kinase deficiency.
Wightman PJ, Jackson GR, Dipple KM. Glycerol hypersensitivity in a Drosophila model for glycerol kinase deficiency is affected by mutations in eye pigmentation genes. PLoS One. 2012;7(3):e31779. Epub 2012 Mar 9. PubMed PMID: 22427807; PubMed Central PMCID: PMC3302884.
The authors used RNAi knockdown and over-expression of Gyk and Dgk in the study, controlling expression of the RNAi reagent and ORFs with the Gal4-UAS system.
The authors indicate that mutations in the eye color genes brown, garnet, rosy, and vermillion, and the body color gene yellow modified glycerol hypersensitivity in the disease model flies.
Glycerol kinase deficiency is described at Wikipedia.
The relevant human genes at NCBI Gene include GK.
GK and the deficiency are described at OMIM.
Orphanet has some info on various forms of the deficiency.
Relevant fly genes include dGyk (Gyk in FlyBase) and dGK (Dgk in FlyBase).
Based on a DIOPT search, at least two other genes have significant similarity to GK, CG8298 and CG7995.
This review looks to be fairly comprehensive and includes comparison of DGKs in model species: Mérida I, Avila-Flores A, Merino E. Diacylglycerol kinases: at the hub of cell signalling. Biochem J. 2008 Jan 1;409(1):1-18. Review. PubMed PMID: 18062770
Thursday, August 2, 2012
Clocks & Neurodisease. Breaking Report.
This study looks at the effect of genetically disrupting circadian rhythms on neurodegeneration, and finds functional ties between the two.
Krishnan N, Rakshit K, Chow ES, Wentzell JS, Kretzschmar D, Giebultowicz JM. Loss of circadian clock accelerates aging in neurodegeneration-prone mutants. Neurobiol Dis. 2012 Mar;45(3):1129-35. PubMed PMID: 22227001; PubMed Central PMCID: PMC3291167.
Mutations in swi and sws are used in the study to model neurodegeneration.
The swi gene appears not to have been well conserved (no strong-scoring matches at DIOPT for example). By contrast, the sws gene has been conserved. The fly sws gene is related to the human gene PNPLA6 (also called NTE; Entrez Gene ID 10908). PNPLA6 is associated with spastic paraplegia 39, one of a group of spastic paraplegias. According to the literature summary at Entrez Gene, the normal role of the PNPLA6 protein is as a phopholipase that deacetyates intracellular phophatidylcholine, producing glycerophophocholine.
Mutations in per are used in the study to disrupt circadian rhythms.
The fly per gene has at least 3 putative orthologs in the human genome, PER1, PER2 and PER3. According to OMIM, mutations in PER2 are associated with familial advanced sleep phase syndrome.
Krishnan N, Rakshit K, Chow ES, Wentzell JS, Kretzschmar D, Giebultowicz JM. Loss of circadian clock accelerates aging in neurodegeneration-prone mutants. Neurobiol Dis. 2012 Mar;45(3):1129-35. PubMed PMID: 22227001; PubMed Central PMCID: PMC3291167.
Mutations in swi and sws are used in the study to model neurodegeneration.
The swi gene appears not to have been well conserved (no strong-scoring matches at DIOPT for example). By contrast, the sws gene has been conserved. The fly sws gene is related to the human gene PNPLA6 (also called NTE; Entrez Gene ID 10908). PNPLA6 is associated with spastic paraplegia 39, one of a group of spastic paraplegias. According to the literature summary at Entrez Gene, the normal role of the PNPLA6 protein is as a phopholipase that deacetyates intracellular phophatidylcholine, producing glycerophophocholine.
Mutations in per are used in the study to disrupt circadian rhythms.
The fly per gene has at least 3 putative orthologs in the human genome, PER1, PER2 and PER3. According to OMIM, mutations in PER2 are associated with familial advanced sleep phase syndrome.
Friday, July 27, 2012
Galactosemia stocks at the BDSC
The Bloomington Drosophila Stock Center has added a Galactosemia page to their Drosophila and Human Disease website. The list of available stocks includes these recently acquired lines from Judy Fridovich-Keil [generated in Sanders et al., 2010, UDP-galactose 4' epimerase (GALE) is essential for development of Drosophila melanogaster. Dis Model Mech. 3:628 PubMed ID 20519568].
37738 w[*]; wg[Sp-1]/CyO; Gale[Deltay]/TM6B, Tb[1]
strong loss of function allele
37739 Gale[h]/TM6B, Tb[1]
hypomorphic allele (weaker than Gale[Deltay]
37740 w[*]; P{UAS-hGALE.S}32A/CyO; TM2/TM6B, Tb[1]
expresses human UDP-galactose 4' epimerase under UAS control
Go to the BDSC's Galactosemia Page.
37738 w[*]; wg[Sp-1]/CyO; Gale[Deltay]/TM6B, Tb[1]
strong loss of function allele
37739 Gale[h]/TM6B, Tb[1]
hypomorphic allele (weaker than Gale[Deltay]
37740 w[*]; P{UAS-hGALE.S}32A/CyO; TM2/TM6B, Tb[1]
expresses human UDP-galactose 4' epimerase under UAS control
Go to the BDSC's Galactosemia Page.
Thursday, July 12, 2012
Galactosemia. Breaking Report.
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