Monday, April 2, 2018

New fly model of mitochondrial disease associated with disruption of SLC25A46

1: Suda K, Ueoka I, Azuma Y, Muraoka Y, Yoshida H, Yamaguchi M. Novel Drosophila model for mitochondrial diseases by targeting of a solute carrier protein SLC25A46. Brain Res. 2018 Mar 28. pii: S0006-8993(18)30163-X. PMID: 29604258.

From the abstract: "Mutations in SLC25A46 gene have been identified in mitochondrial diseases that are sometimes classified as Charcot-Marie-Tooth disease type 2, optic atrophy and Leigh syndrome. Human SLC25A46 functions as a transporter across the outer mitochondrial membrane. However, it is still unknown how the neurodegeneration occurring in these diseases relates to the loss of SLC25A46 function. Drosophila has CG5755 (dSLC25A46) as a single human SLC25A46 homolog. Here we established pan-neuron specific dSLC25A46 knockdown flies, and examined their phenotypes. ... The dSLC25A46 knockdown fly ... recapitulates most of the phenotypes in mitochondrial disease patients, providing a useful tool to study these diseases."

Drosophila analysis helps point to changes in the human gene VPS13D as the cause of a newly identified type of ataxia

Seong E, Insolera R, Dulovic M, Kamsteeg EJ, Trinh J, Brüggemann N, Sandford E, Li S, Ozel AB, Li JZ, Jewett T, Kievit AJA, Münchau A, Shakkottai V, Klein C, Collins C, Lohmann K, van de Warrenburg BP, Burmeister M. Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects. Ann Neurol. 2018 Mar 31. PMID: 29604224.

From the abstract: "... In an international collaboration, we independently performed exome sequencing in seven families with recessive ataxia and/or spastic paraplegia. To evaluate the role of VPS13D mutations, we evaluated a Drosophila knock-out model and investigated mitochondrial function in patient-derived fibroblast cultures. ... Our study demonstrates that compound heterozygous mutations in VPS13D cause movement disorders along the ataxia-spasticity spectrum, making VPS13D the fourth VPS13 paralog involved in neurological disorders. This article is protected by copyright. All rights reserved."

Friday, March 23, 2018

Review article -- Drosophila as a model to study diabetes

Murillo-Maldonado JM, Riesgo-Escovar JR. Development and diabetes on the fly. Mech Dev. 2017 Apr;144(Pt B):150-155. PMID: 27702607.

From the abstract: "... Genetic model organisms, like the common fruit fly, Drosophila melanogaster, offer the possibility of studying the panoply of life processes in normal and diseased states like diabetes mellitus, from a plethora of different perspectives. ..."

Experiments in the fly help identify a genetic cause of primary ovarian insufficiency

Chen A, Tiosano D, Guran T, Baris HN, Bayram Y, Mory A, Shapiro-Kulnane L, Hodges CA, Coban Akdemir Z, Turan S, Jhangiani SN, van den Akker F, Hoppel CL, Salz HK, Lupski JR, Buchner DA. Mutations in the mitochondrial ribosomal protein MRPS22 lead to primary ovarian insufficiency. Hum Mol Genet. 2018 Mar 16. PMID: 29566152.

From the abstract: "Primary ovarian insufficiency (POI) is characterized by amenorrhea and loss or dysfunction of ovarian follicles prior to the age of 40. ... the genetic etiology of POI most often remains unknown. Here we report MRPS22 homozygous missense variants ... identified in four females ... as a novel genetic cause of POI in adolescents. Both missense mutations identified in MRPS22 are rare, occurred in highly evolutionarily conserved residues, and are predicted to be deleterious to protein function. .... Furthermore, we demonstrate in a Drosophila model that mRpS22 deficiency specifically in somatic cells of the ovary had no effect on fertility, whereas flies with mRpS22 deficiency specifically in germ cells were infertile and agametic, demonstrating a cell autonomous requirement for mRpS22 in germ cell development. These findings collectively identify that MRPS22 ... is critical for ovarian development and may therefore provide insight into the pathophysiology and treatment of ovarian dysfunction."

Wednesday, March 21, 2018

Why Fruit Flies Are the New Lab Rats | Essay | Zócalo Public Square

Why Fruit Flies Are the New Lab Rats | Essay | Zócalo Public Square: Set out a bowl of fruit, and they will arrive: small, buff-colored flies with garnet eyes and an attraction to fermenting bananas. Annoying but not harmful ...

Friday, March 16, 2018

Fly models of kidney disease: Drosophila nephrocytes "represent a novel and easy-to-use alternative in experimental nephrology"

Helmstädter M, Simons M. Using Drosophila nephrocytes in genetic kidney disease. Cell Tissue Res. 2017 Jul;369(1):119-126. PMID: 28401308.

The abstract: "Renal diseases are a growing health burden, and innovative models to study their pathomechanisms are greatly needed. Here, we highlight how the fruit fly Drosophila melanogaster can be used to model kidney diseases. We focus on the nephrocyte that has recently been shown to exhibit podocyte and proximal tubular cell features. These cells can be manipulated with precise genetic tools to dissect filtration and reabsorption mechanisms. Thus, they represent a novel and easy-to-use alternative in experimental nephrology."

Wednesday, February 28, 2018

Fly studies contribute to identification pathogenic variant in individuals with lethargy, acidosis, aciduria, hyperammonemia

Oláhová M, Yoon WH, Thompson K, Jangam S, Fernandez L, Davidson JM, Kyle JE, Grove ME, Fisk DG, Kohler JN, Holmes M, Dries AM, Huang Y, Zhao C, Contrepois K, Zappala Z, Frésard L, Waggott D, Zink EM, Kim YM, Heyman HM, Stratton KG, Webb-Robertson BM; Undiagnosed Diseases Network, Snyder M, Merker JD, Montgomery SB, Fisher PG, Feichtinger RG, Mayr JA, Hall J, Barbosa IA, Simpson MA, Deshpande C, Waters KM, Koeller DM, Metz TO, Morris AA, Schelley S, Cowan T, Friederich MW, McFarland R, Van Hove JLK, Enns GM, Yamamoto S, Ashley EA, Wangler MF, Taylor RW, Bellen HJ, Bernstein JA, Wheeler MT. Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder. Am J Hum Genet. 2018 Feb 16. pii: S0002-9297(18)30042-9. PMID: 29478781.

From the abstract: "... Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. ... Knockdown of Drosophila ATPsynδ, the ATP5F1D homolog, in developing eyes and brains caused a near complete loss of the fly head, a phenotype that was fully rescued by wild-type human ATP5F1D. In contrast, expression of the ATP5F1D c.245C>T and c.317T>G variants rescued the head-size phenotype but recapitulated the eye and antennae defects seen in other genetic models of mitochondrial oxidative phosphorylation deficiency. Our data establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation."