A TRANSGENIC MOUSE LINE HARBORING A SMOOTH-MUSCLE ALPHA-ACTIN PROMOTER POLYOMAVIRUS MIDDLE T-ANTIGEN TRANSGENE DEVELOPS AN EPITHELIAL HYPERPLASIA IN THE RECTUM AND DISTAL STOMACH

BACKGROUND: Transgenic mice are the product of the microinjection of f oreign DNA directly into the pronuclei of a one-cell embryo. The forei gn DNA can cause insertional inactivation or activation of the flankin g genetic locus. EXPERIMENTAL DESIGN: We isolated five lines of transg enic mice harboring the chicken alpha-actin vascular smooth muscle enh ancer/promoter linked to the polyomavirus middle T antigen using a sta ndard microinjection protocol. The expression of the transgene was ass essed in RNA prepared from affected and nonaffected tissue by RNase pr otection and reverse transcriptase-polymerase chain reaction analyses. Cell morphology was determined in stained sections from fixed tissues . RESULTS: In this article, we document the development of epithelial hyperplasia in the rectum and distal stomach together with female infe rtility in a single line of transgenic mice harboring the transgene. W e were unable to demonstrate the expression of the transgene in any ti ssue examined, regardless of the degree of hyperplasia. The phenotype was present in the heterozygous state in both males and females. CONCL USIONS: In the absence of the expression of the transgene, we conclude that the insertion of the transgene may have caused the epithelial hy perplasia directly or may have contributed to a condition that promote s hyperplasia. The transgene may have activated a dominant-acting neig hboring gene.