Studies on the regulation of renin genes using transgenic mice

Transgenic mice are being used as an assay to identify the DNA sequences that direct the tissue specificity and physiological regulation of murine renin gene expression. In initial studies, a DNA segment encoding the duplicated renin gene, Ren-2, has been injected into the pronuclei of fertilized eggs homozygous for the Ren-1c allele. The 24 kb XhoI fragment utilized consists of 5.3 kb of upstream flanking sequences and 9.5 kb of 3' flanking sequence in addition to the 10 kb segment encoding the 9 exons of the natural gene. Seventeen transgenic founder mice were identified of which at least 7 exhibited evidence of transgene expression. The 4 expressing lines that have been studied in detail integrated from 5 to 15 copies of the transgene but expression was not proportional to the number of copies integrated. Qualitatively, expression is detected in the correct spectrum of tissues, and submandibular gland expression of the transgene responds appropriately to known hormonal modulators. However, quantitatively, the levels of expression deviate considerably from normal.