Monday, July 9, 2018

Fruit flies and kidney disease -- a review and a research article

Millet-Boureima C, Porras Marroquin J, Gamberi C. Modeling Renal Disease "On the Fly". Biomed Res Int. 2018 May 31;2018:5697436. doi: 10.1155/2018/5697436. eCollection 2018. Review. PubMed PMID: 29955604; PubMed Central PMCID: PMC6000847.

Abstract: "Detoxification is a fundamental function for all living organisms that need to excrete catabolites and toxins to maintain homeostasis. Kidneys are major organs of detoxification that maintain water and electrolyte balance to preserve physiological functions of vertebrates. In insects, the renal function is carried out by Malpighian tubules and nephrocytes. Due to differences in their circulation, the renal systems of mammalians and insects differ in their functional modalities, yet carry out similar biochemical and physiological functions and share extensive genetic and molecular similarities. Evolutionary conservation can be leveraged to model specific aspects of the complex mammalian kidney function in the genetic powerhouse Drosophila melanogaster to study how genes interact in diseased states. Here, we compare the human and Drosophila renal systems and present selected fly disease models."

Hermle T, Schneider R, Schapiro D, Braun DA, van der Ven AT, Warejko JK, Daga A, Widmeier E, Nakayama M, Jobst-Schwan T, Majmundar AJ, Ashraf S, Rao J, Finn LS, Tasic V, Hernandez JD, Bagga A, Jalalah SM, El Desoky S, Kari JA, Laricchia KM, Lek M, Rehm HL, MacArthur DG, Mane S, Lifton RP, Shril S, Hildebrandt F. GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome. J Am Soc Nephrol. 2018 Jun 29. pii: ASN.2017121312. doi: 10.1681/ASN.2017121312. [Epub ahead of print] PubMed PMID: 29959197.

From the abstract: "... Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of CKD. The discovery of monogenic causes of SRNS has revealed specific pathogenetic pathways, but these monogenic causes do not explain all cases of SRNS. ... To identify novel monogenic causes of SRNS, we screened 665 patients by whole-exome sequencing. We then evaluated the in vitro functional significance of two genes and the mutations therein that we discovered through this sequencing and conducted complementary studies in podocyte-like Drosophila nephrocytes. ... In Drosophila, silencing Gapvd1 impaired endocytosis and caused mistrafficking of the nephrin ortholog. ... Mutations in GAPVD1 and probably in ANKFY1 are novel monogenic causes of NS. The discovery of these genes implicates RAB5 regulation in the pathogenesis of human NS."

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