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 foreign DNA directly into the pronuclei of a one-cell embryo. The foreign DNA can cause insertional inactivation or activation of the flanking genetic locus. EXPERIMENTAL DESIGN: We isolated five lines of transgenic mice harboring the chicken alpha-actin vascular smooth muscle enhancer/promoter linked to the polyomavirus middle T antigen using a standard microinjection protocol. The expression of the transgene was assessed in RNA prepared from affected and nonaffected tissue by RNase protection 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 infertility in a single line of transgenic mice harboring the transgene. We were unable to demonstrate the expression of the transgene in any tissue examined, regardless of the degree of hyperplasia. The phenotype was present in the heterozygous state in both males and females. CONCLUSIONS: In the absence of the expression of the transgene, we conclude that the insertion of the transgene may have caused the epithelial hyperplasia directly or may have contributed to a condition that promotes hyperplasia. The transgene may have activated a dominant-acting neighboring gene.