Knockout mice phenotyping

Emmen, J.M. and Korach, K.S. (2003) Estrogen receptor knockout mice phenotypes in the female reproductive tract Gynecological Endocrinology, 17, 169-176. 

Figure 5. Network illustration of protein interactions and knockout mouse phenotype in PSP proteins. 650 protein-protein interactions for 281 PSP proteins are shown. These PSP interactions are divided into MASC (Red circle), cPSD (Blue circle) and nodes outside the circles are other components of the Total PSD. Also, a Venn diagram of the total numbers of proteins in the MASC, cPSD and Total PSD is shown. Proteins in this network for which an electrophysiological phenotype (change in LTP/LTD) has been reported in the literature are indicated by green nodes. The size of a node is proportional to its connectivity (number of interactors) and it can be seen that the largest nodes with an electrophysiological phenotype are in MASC.

In finalizing this series of studies, the double receptor knockout mouse (OX,k / ()X2k ) was shown to be phenotypically indistinguishable from orexin mice (Kisanuki et al, 2001), a result that makes the existence of additional orexin receptors unlikely. 

Li 1, Patil RV, Verkman AS (2002) Mildly abnormal retinal function in transgenic mice without Muller cell aquaporin-4 water channels. Invest Ophthalmol Vis Sci 43 573—579 Ma T, Yang B, Gillespie A, Carlson El, Epstein Cl, Verkman AS (1997) Generation and phenotype of a transgenic knockout mouse lacking the mercurial-insensitive water channel aquaporin-4. 1 Clin Invest 100 957-962... 

The results of knockout mouse studies indicate that caspase function can be divided into two broad phenotypic classes, those that have primary crucial effect on animal development (proapoptotic caspases, i.e., caspase-3, -7, -8, and -9) and those that mediate immune system functions (proinflammatory caspases, i.e., caspase-1 and -11) [64, 73]. 

Steele AD, Lindquist S, Aguzzi A (2007) The prion protein knockout mouse a phenotype under challenge. Prion 1 83... 

The recent finding that an NPY knockout mouse maintained a normal phenotype (Erickson et al., 1996) may indicate that when NPY is absent from an embryonic stage, alternative pathways can compensate for such a deficiency. 

This table lists the major classes of eicosanoid receptors and dieir signaling characteristics. Splice variants are indicated where appropriate. Major phenotypes in knockout mouse models are listed. 

Gros The mouse is a good model in that mutations in specific pathways cause the same phenotypes as homologous mutations do in humans. Although the ultimate effector mechanism may be different, the regulatory networks are Ukely to be preserved. In addition, macrophages may have many ways to kill TB. The IFNy knockout mouse dies within three weeks of TB infection. Although such a rapid death is probably linked to the experimental model used (which in this case does not mirror human TB in the field), the very deleterious effect of absence of IFNy on host response to TB is clearly vaUdated in both mouse and humans. 

In summary, gene knockout mouse technology has allowed us to determine the function of cell surface carbohydrates in mouse embryos in recent years. Some glycosyltransferases-deficient mutant mouse showed severe phenotypes, including embryonic lethality. However, we have not yet identified the mechanisms underlying these phenotypes. Identification of critical carbohydrate structure (s), specific proteins carrying specific carbohydrate structure(s), and the counter-receptors for those carbohydrates should be identified in future studies. 

A study by researchers at Lexicon Genomics (now Lexicon Pharmaceuticals) looked at the targets for the top 100 prescription drugs and found that for the targets where knockout models could be generated (most of them) in 85% of the cases the knockouts produced phenotypes that were informative for the therapeutic indication involved. Not only Lexicon but also National Institutes of Health NIH) has now embarked on projects aimed at knocking out most if not all of the genes found in mouse. ... 

The outcome of a CPTIB knockout study will provide answers to existing questions. It can be e qiected that new questions will arise as well, and that basic scientific insight may gain considerably. One of the major reasons to develop a conditional knockout mouse model for both CPTl genes is to investigate the phenotype of a M-CPTl defect as a single entity, as well as in conjunction with a L-CPTl defect. 

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