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Transgenic and gene knockout techniques allow for in vivo study of the consequences of adding or subtracting specific genes. However, in some instances, such as the study of lethal mutations or of the physiological consequences of changing gene expression, turning on and off an introduced gene at will would be advantageous. We have used cytochrome p450 1A1 promoter to drive expression of the human apolipoprotein E (apoE) gene in transgenic mice. In six independent lines, robust expression of the transgene depended upon injection of the inducer [beta]-naphthoflavone, whereas the seventh line had high basal expression that was augmented further by the inducer. The low level of basal expression in an inducer-dependent line was confirmed upon breeding the transgene onto the hypercholesterolemic apoE-deficient background. In the basal state transgene expression was physiologically insignificant, as these mice were as hypercholesterolemic as their nontransgenic apoE-deficient littermates. When injected with the inducer, plasma cholesterol levels of the transgenic mice decreased dramatically as apoE expression was induced to yield greater than physiological levels in plasma. The inducer could pass transplacentally from an injected mother to her fetuses with concomitant induction of fetal transgene mRNA. Inducer could also pass via breast milk from an injected mother to her suckling neonatal pups, giving rise to the induction of human apoE in neonate plasma. These finding suggest a strategy to temporarily ameliorate genetic deficiencies that would otherwise lead to fetal or neonatal lethality.

Electrolytic systems containing a platinum electrode and a redox mediator with purified recombinant proteins containing P450A1 are applicable to various P450s for the synthesis of stereo and regio-specific hydroxylated products. Experimental results show that NADPH can be replaced by these systems for the electrocatalytically mediated omega-hydroxylation of lauric acid.

The rat liver microsome-catalyzed oxidation of n-butyraldoxime yields two volatile metabolites, nitrobutane and n-butyronitrile. The latter's formation via a Beckmann-type dehydration is unprecedented. Evidence suggests that the process is catalyzed by cytochrome P-450 through the interaction of its ferrous iron with the oxime's oxygen atom. The conversion is also unique in that the nitrile retains the oxime's original carboskeleton, in contrast to other Beckmann dehydration reactions. While n-butyraldoxime is known to inhibit hepatic aldehyde dehydrogenase, neither n-butyronitrile nor nitrobutane does so, suggesting other means of bioactivation for the oxime.