Here we identify components of the CCR4-NOT complex as novel regulators ensuring repression of the MHC II locus, as revealed by various loss-of-function models in cells and animals.
Various loss-of-function models, including genetic knockout, pharmacological blockade and selective chemical knockout, confirmed contributions of each constituent activity in vivo.
In addition, the effects of gene knockdown can be assessed using various loss-of-function mutants, and researchers recently developed a new method of generating loss-of-function mutations in targeted genes in C. elegans [ 2].
To identify downstream components of phyB signaling, various loss-of-function genetic approaches have been used, including the identification of mutants that either mimic or suppress phyB-null phenotypes (Reed et al. 1998, 2000).
Firstly, in contrast to the situation described for miRNAs in lower vertebrates, the effects of individual miRNAs on mRNA and protein processing in mammals are relatively modest, as judged by the results of various loss-of-function studies [ 19].
Various loss-of-function mutations in p53 and/or pRB tumor-suppressor genes have been found in osteosarcoma and both tumor suppressors have been linked to the expression and/or activity of Runx2.
Various loss-of-function mutations of ATP6V0A2 [Ensembl:ENSCAFG00000007234], which encodes the alpha-2 subunit of the V-type H+ ATPase, resulting in impaired glycosilation of proteins during synthesis cause autosomal recessive cutis laxa (ARCL) type II [OMIM 219200] and some cases of wrinkly skin syndrome [OMIM 278250] [ 16].
Mutant mitochondrial tRNAs frequently induce various loss-of-function at a molecular level [ 2] including not only damaged mitochondrial protein synthesis, but also inhibited aminoacylation [ 3], tRNA molecular instability [ 4], altered tRNA processing [ 5], wobble-base modification deficiency [ 6, 7], or a combination of these.
Among the various loss of flow situations possible in a fast reactor, rupture of coolant pipe is very important due to the rapid reduction in coolant flow resulted under this condition.
