Knockout animal

Knockout animal studies, in contrast to the above methods, are dependent upon phenotype observation. The approach entails the generation and study of mice in which a specific gene has been deleted. Phenotypic studies can sometimes yield clues as to the function of the gene knocked out. 

Siarim, M. and Krishnamurthy, H. 2001. The role of follicle stimulating hormone in spermatogenesis lessons from knockout animal models. Archives of Medical Research 32(6), 601-608. 

The role of GPR55 is unknown at present. Transcripts have been identified in various human tissues, including brain, spleen, ileum and omental (but not subcutaneous) adipose tissue. This last observation may point to a role in regulation of central adiposity, but blood pressure control has also been suggested as a possible function [88]. Specific ligands and/or knockout animals will be required to probe further the role of this receptor. 

A variation of this tedinique produces a knockout animal, in which a normal gene has been functionally eliminated. This maybe done by site-specific mutagenesis. 

Knockout animals have a normal gene intentionally inactivated/destroyed. 

Ti-ansgenic and knockout animals are used as models of human disease. 

The best evidences are studies from preclinical animal models [86, 87, 105], or knockout animals lacking appropriate anti-oxidative pathways [106]. For example, Balb/c mice administered a variety of anti-oxidants in their chow were protected from acetaminophen hepatotoxicity [107]. Rats fed with the anti-oxidant melatonin were protected from cholesterol mediated oxidative liver damage [108]. The best clinical evidence that oxidative stress is a key player in a variety of liver injury diseases is the beneficial application of silymarin in these disease indications [109]. Silymarin is a polyphenolic plant fiavonoid (a mixture of flavonoid isomers such as silibinin, isosilibinin, silidianin and silichristin) derived from Silymarin maria-num that has antioxidative, antilipid peroxidative, antifibrotic and anti-inflammatory effects [109, 110]. 

Schibkr No. The valley is much wider in the wild-type as opposed to the knockout animals, because it is only repressed when REV-ERBa is active during that narrow window. 

It is interesting to note that pharmacological blockage of NKl receptors also revealed anxiolytic effects in the plus-maze test when mice from the 129/Sv strain (Santarelh et al. 2001), but not from other strains (Rodgers et al. 2004), were used. Thus, the anxiolytic effect of NKl receptor antagonists seems to be more sensitive to effects of the genetic background as compared to benzodiazepines. It is also possible that the relative contribution of the SP-NK1 system in the modulation of anxiety is situation dependent. The basal corticosterone levels in the blood plasma of NKIR and NK1 mice do not differ in low-stress situations, but the increase after the stressful elevated plus-maze test is blunted in the knockout animals (Santarelh et al. 2001). 

Muscarinic stimulants contract the smooth muscle of the bronchial tree. In addition, the glands of the tracheobronchial mucosa are stimulated to secrete. This combination of effects can occasionally cause symptoms, especially in individuals with asthma. The bronchoconstriction caused by muscarinic agonists is eliminated in knockout animals in which the M3... 

Taken together there is some direct proof for a functional contribution of spinal NMDA receptors in the process of induction of hyperalgesia by conditional spinal NR1 knockout animals or spinal NR1 knock-down experiments. While at least indirect evidence suggests a correlation between upregulation of the NMDA receptor activity and nociception, the interpretation of the impact of knocking out NR2 subunits needs further detailed research. 

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