Wednesday, November 8, 2017

Fly research helps inform understanding of signal pathway roles in Schimke immuno-osseous dysplasia

Morimoto M, Myung C, Beirnes K, Choi K, Asakura Y, Bokenkamp A, Bonneau D, Brugnara M, Charrow J, Colin E, Davis A, Deschenes G, Gentile M, Giordano M, Gormley AK, Govender R, Joseph M, Keller K, Lerut E, Levtchenko E, Massella L, Mayfield C, Najafian B, Parham D, Spranger J, Stenzel P, Yis U, Yu Z, Zonana J, Hendson G, Boerkoel CF. Increased Wnt and Notch signaling: a clue to the renal disease in Schimke immuno-osseous dysplasia? Orphanet J Rare Dis. 2016 Nov 5;11(1):149. PMID: 27816064; PMCID: PMC5097426.

From the abstract: "Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder caused by biallelic mutations in the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily A-like 1 (SMARCAL1) gene. ... we hypothesized that SMARCAL1 deficiency causes the focal segmental glomerulosclerosis (FSGS) of SIOD by altering renal gene expression. We tested this hypothesis by gene expression analysis of an SIOD patient kidney and verified these findings through immunofluorescent analysis in additional SIOD patients and a genetic interaction analysis in Drosophila. ... We conclude that increased Wnt and Notch activity result from SMARCAL1 deficiency and, as established causes of FSGS, contribute to the renal disease of most SIOD patients. This further clarifies the pathogenesis of SIOD and will hopefully direct potential therapeutic approaches for SIOD patients."

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