Inactivation of the gene

Ninkina, N. et al. Neurons expressing the highest levels of y-synuclein are unaffected by targeted inactivation of the gene. Mol. Cell. Biol. 23 8233-8245, 2003. 

Link RE, Stevens MS, Kulatunga M, Scheinin M, Barsh GS, Kobilka BK (1995) Targeted inactivation of the gene encoding the mouse a2c-adrenoceptor homolog. Mol Pharmacol 48 48-55... 

It has recently been reported that cytochrome bj is required for full activity of F3 /5 H. The gene encoding this protein, difF, was cloned from petunia42 and shown to be exclusively expressed in flowers generating purple or blue petals. Inactivation of the gene reduced both F3 /5 H activity and 5 -substituted pigments, thus resulting in altered flower color.42... 

Jalbert LR, Rosen ED, Moons L et al. (1998) Inactivation of the gene for anticoagulant protein C causes lethal perinatal consumptive coagulopathy in mice. J Clin Invest 102 1481-1488... 

The inactivation of the genes of the sex chromosomes, and of some of the genes of numbered chromosomes, results, in part, from the attachment of methyl groups (—CHj) to the DNA. Methyl group attachment is thought to be the only type of intentional alteration to the chemistry of human DNA. The methyl groups attached to our DNA reside on residues of cytosine. 

Fig. 4.1 Gene disruption by targeted mutation. To delete exon 2 (E2), a targeting construct was prepared with side arms containing homologous DNA upstream and downstream of exon 2, respectively. By recombination events in the upstream and downstream arms, exon 2 and part of the surrounding intronic region will be replaced by a neomycin selection cassette (neo), resulting in the inactivation of the gene.

Putaala H, Soininen R, Kilpelainen P, Wartiovaara J, Tryggvason K. The murine nephrin gene is specifically expressed in kidney, brain and pancreas inactivation of the gene leads to massive proteinuria and neonatal death. Hum Mol Genet 2001 10 1-... 

This technique employs site-specific DNA recombination sites (called loxP sites) and the enzyme Cre that catalyzes recombination between them. The loxP-Cre recombination system is derived from bacteriophage P1, but this site-specific recombination system also functions when placed in mouse cells. An essential feature of this technique is that expression of Cre is controlled by a cell-type-speclflc promoter. In loxP-Cre mice generated by the procedure depicted in Figure 9-40, inactivation of the gene of Interest (X) occurs only in cells in which the promoter controlling the cre gene is active. 

O-acetyl-L-serine (thiol)-lyase A (CysK), O-acetyl-L-serine (thiol)-lyase B (CysM) and MalY. Thus in order to engineer a potent L-cysteine over-producer excessive degradation of the amino acid must be prevented by inactivation of the genes encoding the major L-cysteine desulfhydrase activities. 

An analysis of the activation-inactivation of the gene for tyrosine aminotransferase has been made in rat hepatoma cell cultures (Martin and Tomkins, 1970). It is known that the synthesis of tyrosine aminotransferase can be induced by glucocorticoids during the latter half of the Gi and S periods of the cell cycle but not during the G2 or early part of the Gi periods. Although the mechanism that is postulated is complex, it involves, in part, the activation and inactivation of genes regulating the synthesis of tyrosine aminotransferase. 

In cultured mammalian cells, thymidine kinase activity is low during the Gi period and increases at the start of the S period of the cell cycle (Stubblefield and Murphree, 1967 Loeb et al., 1970), reaches a maximum during the S period, remains elevated through the G2 period, and decreases abruptly at the end of mitosis (Stubblefield and Murphree, 1967 Thilly et al., 1975 Howard et al., 1974 Bello, 1974). This would appear to represent activation-inactivation of the gene for thymidine kinase. 

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