An orally available compound identified by high-throughput screening, the CFTR potentiator VX-770 (Ivacaftor, trade name Kalydeco), has been shown to efficiently reduce chloride levels in sweat and to improve lung function in CF patients harboring the G551D CFTR genotype, a rare class III CFTR mutant that affects only 4 5%% of CF patients [7, 8].
Additionally, the host has a modifier locus with two possible alleles, m (wildtype) and M (mutant), that affect the recombination rate.
Although most mutants affecting cilial morphology or function lead to a decrease in Shh pathway function, such as seen in the IFT52, IFT57, IFT88/polaris, IFT172 and Kif3a mutants (66– 69, 72, 73), at least one mutant that affects retrograde intraflagellar transport results in activation of the Shh pathway (42).
This validates that the positive genetic selection for mutants impaired in light/carbon repression of ASN1::HPT2 enabled us to isolate an Arabidopsis mutant that affects the light/carbon regulation of genes involved in metabolism and other genes in related energy pathways.
An orally available compound identified by high-throughput screening, the CFTR potentiator VX-770 (Ivacaftor, trade name Kalydeco, Vertex Pharmaceuticals), efficiently reduces chloride levels in sweat and improves lung function in CF patients harboring the CFTR G551D genotype, a rare class III CFTR mutant that affects only 4%to5%5% of CF patients worldwide.
To investigate the contribution of some of the cellular translation factors on ribosome rescuing, we provoked stalling at AGA codons in mutants that affected the factors and then analyzed the accumulation of oligopeptidyl (peptides of up to 6 amino acid residues, oligopep- -tRNA oligopep- -tRNA (peptides oligopep- -tRNA0 aminoracids in length, polypeptidylNA associated with ribosomes.
The screen for yeast mutants that affected Adr1 phosphorylation used a subset of 102 strains from the MATa yeast gene deletion collection (Invitrogen) that encode protein kinases according to the Saccharomyces Genome Database (yeastgenome.org).org
Around that time, Mike met Len Zon, who was doing screens in zebrafish to identify genetic mutants that affected the cell cycle.
As controls, we used the parental strain of the knockouts as well as two slow-growing mutants that affected the sETC, cya-5-34 (Nargang et al. 1978), and [ mi-3] (Mitchell et al. 1953).
To determine the pathogenic role of elevated IGFBP5, we established transgenic mouse lines in which IGFBP5 is overexpressed specifically in neurons under the control of the neurofilament-light chain (NF-L) promoter and found a progressive neuropathy in these mutants that affected both sensory and motor nerve fibers.
