Genetic compensation: A phenomenon in search of mechanisms.
TLDR
This review revisits studies reporting genetic compensation in higher eukaryotes and outlines possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.Abstract:
Several recent studies in a number of model systems including zebrafish, Arabidopsis, and mouse have revealed phenotypic differences between knockouts (i.e., mutants) and knockdowns (e.g., antisense-treated animals). These differences have been attributed to a number of reasons including off-target effects of the antisense reagents. An alternative explanation was recently proposed based on a zebrafish study reporting that genetic compensation was observed in egfl7 mutant but not knockdown animals. Dosage compensation was first reported in Drosophila in 1932, and genetic compensation in response to a gene knockout was first reported in yeast in 1969. Since then, genetic compensation has been documented many times in a number of model organisms; however, our understanding of the underlying molecular mechanisms remains limited. In this review, we revisit studies reporting genetic compensation in higher eukaryotes and outline possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.read more
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Kir6.1-dependent KATP channels in lymphatic smooth muscle and vessel dysfunction in mice with Kir6.1 gain-of-function.
Michael J. Davis,Hae Jin Kim,Scott D. Zawieja,Jorge A. Castorena-Gonzalez,Peichun Gui,Min Li,Brian Saunders,Bernd H. Zinselmeyer,Gwendalyn J. Randolph,Maria S. Remedi,Colin G. Nichols +10 more
TL;DR: The high sensitivity of LSM to KATP channel GoF offers an explanation for the lymphoedema observed in patients with Cantú syndrome, a disorder caused by gain‐of‐function mutations in genes encoding Kir6.1 or SUR2, and suggests that glibenclamide may be an appropriate therapeutic agent.
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Combined shRNA over CRISPR/cas9 as a methodology to detect off-target effects and a potential compensatory mechanism.
Liat Peretz,Elazar Besser,Renana Hajbi,Natania Casden,Dan Ziv,Nechama Kronenberg,Liat Ben Gigi,Sahar Sweetat,Saleh Khawaled,Rami I. Aqeilan,Oded Behar +10 more
TL;DR: A combination of RNA inhibition and CRISPR/cas9 methods to identify possible off targets as well as potential compensatory effects are presented and it is clearly demonstrated that the Sema4B targeted shRNA effects on cell proliferation is the result of off-target effects.
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Fishing forward and reverse: Advances in zebrafish phenomics.
TL;DR: The genetic and quantitative tools available in the zebrafish model, coupled with the broad spectrum of phenotypes that can be assayed, make it a powerful model for phenomics, well suited for the dissection of genotype-phenotype associations in development, physiology, health and disease.
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Autism-associated SHANK3 mutations impair maturation of neuromuscular junctions and striated muscles
Anne-Kathrin Lutz,Stefanie Pfaender,Berra Incearap,Valentin Ioannidis,Ilaria Ottonelli,Karl J. Föhr,Judith Cammerer,Marvin Zoller,Julia Higelin,Federica Giona,Maximilian Stetter,Nicole Stoecker,Najwa Ouali Alami,Michael Schön,Michael Orth,Stefan Liebau,Gotthold Barbi,Andreas M. Grabrucker,Richard Delorme,Michael Fauler,Benjamin Mayer,Sarah Jesse,Francesco Roselli,Albert C. Ludolph,Thomas Bourgeron,Chiara Verpelli,Maria Demestre,Tobias M. Boeckers +27 more
TL;DR: The results suggest that the hypotonia in SHANK3 deficiency might be caused by dysfunctions in all elements of the voluntary motor system: motoneurons, neuromuscular junctions (NMJs), and striated muscles.
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Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications
TL;DR: The mechanisms of albumin reabsorption, catabolism and transcytosis are being reexamined utilizing techniques that allow for novel molecular and cellular discoveries including discussing genetic disorders and therapeutic considerations.
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