Knockout studies

Inhibition of cytokine activity in vivo by administration of monoclonal antibodies (and, more recently, by gene knockout studies) continues to elucidate the physiological and pathophysiological effect of various cytokines. 

Raeymaekers L, Wuytack F 1996 Calcium Pumps. In Barany M (ed) Biochemistry of smooth muscle contraction. Academic Press, New York, p 241-253 Shull GE 2000 Gene knockout studies of Ca2+-transporting ATPases. Eur J Biochem 267 5284-5290... 

Despite the obvious expression of GABAb receptors in many peripheral organs, such as heart, spleen, lung, liver, intestine, stomach, and urinary bladder, no overt peripheral phenotype has been described for GABAB(1)-deficient mice. However, as in the central nervous system (CNS), knockout studies demonstrate that the GABAB(i) subunit is an essential requirement for GABAb receptor function in the enteric and peripheral nervous system (PNS) (66). 

Knockout studies in mice revealed that the loss of H2A.X causes an increased frequency of chromosomal rearrangements, which often result in oncogenic transfer-... 

At last, nucleolin might play a specific role in telomeric replication and maintenance, as suggested by two types of data. First, it binds telomeric repeat (TTAGGG)n in vitro (Ishikawa et al, 1993 Pollice et al, 2000), with a marked preference for the single-stranded form. Secondly, it interacts in vitro and in vivo with hTERT (Khurts et al, 2004), the protein catalytic component of human telom-erase. This interaction takes place both in the cytoplasm and in the nucleolus, where it could promote the assembly of hTERT with the RNA subunit hTERC. As a conclusion, many data regarding the involvement of nucleolin in DNA replication are indirect and an experimental demonstration through knockdown or knockout studies is still awaited. 

PRMTl, a nuclear receptor coactivator, exists as in a 330 kDa complex and is a H4 Arg-3 methyltransferase [133,215]. The enzyme appears to be a chromatin bound, and evidence from immunodepletion and knockout studies suggest that it is the principle, if not sole, H4 Arg-3 methyltransferase [133,215]. Mutation of the S-adenosyl methionine binding site in PRMTl annihilated its nuclear receptor coactivator activity with the androgen receptor, providing evidence for the importance of the methylation event in gene expression [215]. Yeast Rmtl, which is homologous to human PRMTl, methylates Arg-3 only in free H4 [208]. 

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been shown to induce cell apoptosis. Through its death domain, this receptor interacts with TRADD protein, which is known to serve as an adaptor that mediates signal transduction of TNF receptors. Knockout studies in mice suggested that this gene plays a role in T-helper cell activation, and may be involved in inflammation and immune regulation. 

Rutter AR, Fradley RL, Garrett EM, Chapman KL, Lawrence JM, et al. 2007. Evidence from gene knockout studies implicates ASC-1 as the primary transporter mediating D-serine reuptake in the mouse CNS. Eur J Neurosci 25 ... 

Knockout studies are being used to inactivate genes in living organisms and monitor any changes that could reveal their functions. 

Some MAPKs have several isoforms that may have different functions. Gene knockout studies have suggested isoform-specific roles. Thus, the development of inhibitors with the ability to interfere with one or a few isoforms as well as those that inhibit all isoforms will be desirable to understand the biology of these enzymes. 

There are four major classes of opioid receptors mu, kappa, delta, and NOP receptors (see http //www.iuphar-db.org/ GPCR/ChapterMenuForv ard chapterID = 1295). Pharmacological studies in many species and knockout studies in mice indicate that the mu opioid receptors (MOP receptors MOR OP receptors) are involved in most of the clinically important effects associated with opioid drugs (Matthes et al., 1996 ... 

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