Tissue-specific expression of the rat β-casein gene in transgenic mice

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Abstract
The rat .beta.-casein gene is a member of a small gene family, encoding the principal milk proteins. In order to understand the mechanisms by which its stage- and tissue-specific expression are regulated, initially, a 14 kb genomic clone containing the entire 7.5 kb rat .beta.-casein gene with 3.5 kb of 5'' and 3.0 kb of 3'' flanking DNA was microinjected into the germline of mice. Eight F0 transgenic mice were generated with copy numbers ranging from 1-10; five transmitted the transgene to their offspring in a Mendelian pattern. A specific RNase protection assay was developed to quantitate the level of expression of the rat .beta.-casein transgene as compared to the endogenous mouse .beta.-casein gene. Using this assay expression was demonstrated predominantly in the lactating mammary gland of transgenic mice at a level of 0.01-1% of the endogenous mouse .beta.-casein gene. The transgene employed the authentic transcription initiation site observed previously in the analogous rat .beta.-casein gene. In one line, a reduced level of expression of the transgene was also observed in the brain. The site of integration, therefore, plays an important role in influencing the level of expression of the transgene, but not its general pattern of tissue-specificity. The transgene appears to be developmentally-regulated in accordance with the endogenous mouse .beta.-casein gene. These lines of mice generated carrying the rat .beta.-casein transgene should provide useful models for studying the developmental and hormonal regulation of milk protein gene expression.