An insulin receptor-like mutant allele (daf-2) with reduced signaling induces dauer formation, and this was enhanced by an OGA null mutant which elevated O-GlcNAc [ 3], and inhibited by an OGT null mutant which reduced O-GlcNAc levels [ 5].
Since Cx26 mutants are strongly correlated with skin disease (hyperkeratosis) [ 43– 45], Cx43 mutants which reduce Cx26 levels may also contribute mechanistically to any resulting skin disease phenotype and also wound repair [ 46].
In contrast, eat-2 mutants, which reduce pharyngeal pumping and are a model of DR in C. elegans, impaired long-term memory in young adults but maintained the memory for longer into older age.
To examine whether decreased degradation had any effect in an in vivo setting, we determined white blood cell (WBC) counts in mice that were first treated with 5FU for 24 h to inhibit haematopoiesis followed by treatment with wild-type G-CSF or mutant G-CSF engineered for increased dissociation at an endosomal pH (mutant D113H), which reduces its degradation through increased recycling.
Thus, we generated myosin-Va mutants that alter the interaction of myosin-Va with F-actin tracks; the switch II mutant G440A, which increases the affinity and stability of myosin-Va interaction with F-actin by two orders of magnitude [ 15]; and the switch I mutant S217A, which reduces the duty ratio of myosin-Va from 0.85 to 0.25 [ 16].
For the latter, double mutant mice were generated by crossing HET mice with transgenic lines expressing the Glu54Lys mutant α-tropomyosin, which reduces myofibrillar Ca2+-sensitivity and leads to dilated cardiomyopathy [ 16, 17], and the Glu180Gly mutant α-tropomyosin, which increases myofibrillar Ca2+ sensitivity and causes hypertrophic cardiomyopathy [ 18, 19].
Mutant Drp1K38A overexpression, which reduces mitochondrial fission, increased mitochondrial length and significantly reduced capsaicin-induced axonal loss from ~50 to ~15 % (Fig. 7d).
Furthermore, an UNC93B1 point mutant (D34A), which reduced TLR9 signaling but enhanced TLR7 signaling (Fukui et al., 2009, 2011), reduced TLR9 transport and cleavage.
Aeration allows better drainage, which reduces runoff.
Certain features of Axd resemble the known pathogenesis in curly tail mutant embryos, in which reduced expression of Grhl3 in the hindgut leads to diminished proliferation and enhanced ventral curvature of the caudal region of the embryo (21).
