0.2 kb promoter sequence of the murine Cyp19 gene target β-galactosidase expression to specific brain areas of transgenic mice

Cyp19 encodes the key enzyme of estrogen biosynthesis, aromatase cytochrome P450. In mice it is mainly expressed in the ovary and brain, where transcription is directed by a distal, brain-specific promoter (Pbr). In order to map functional sequence elements of Pbr, portions of various length (0.2, 1.0, and 1.7 [kb]) were fused to a lacZ reporter gene and analyzed in transgenic mice. Numbers of integrated reporter genes varied from 1 to 23 copies in different transgenic lines. These copy numbers however did not show any correlation to the levels of transgene expression. All of the constructs were found being expressed in the olfactory bulb, limbic cortex, amygdala, and hypothalamus. Additional expression in thalamic nuclei, bed nucleus of stria terminalis, and dorsal mesencephalon was found in transgenic lines with constructs 1.0 and 1.7, and expression in septal and preoptic nuclei was only found with construct 1.7. The data demonstrate that 0.2 kb of Pbr target reporter gene expression to specific brain areas. The data also strongly suggest that the sequence between 0.2 and 1.7 kb upstream, is necessary for expression in additional areas. However even 1.7 kb of Pbr are not sufficient to consistently mimic the accurate expression pattern of Cyp19.