VARIEGATED TRANSGENE EXPRESSION IN MOUSE MAMMARY-GLAND IS DETERMINED BY THE TRANSGENE INTEGRATION LOCUS

Mice carrying an ovine beta-lactoglobulin (BLG) transgene secrete BLG protein into their milk. To explore transgene expression stability, we studied expression levels in three BLG transgenic mouse lines. Unexpe ctedly, two lines exhibited variable levels of transgene expression. C opy number within lines appeared to be stable and there was no evidenc e of transgene rearrangement. In the most variable line, BLG productio n levels were stable within individual mice in two successive lactatio ns. Backcrossing demonstrated that genetic background did not contribu te significantly to variable expression. Tissue in situ hybridization revealed mosaicism of transgene expression within individual mammary g lands from the two variable lines; in low expressors, discrete patches of cells expressing the transgene were observed. Transgene protein co ncentrations in milk reflected the proportion of epithelial cells expr essing BLG mRNA. Furthermore, chromosomal in situ hybridization reveal ed that transgene arrays in both lines are situated close to the centr omere. We propose that mosaicism of transgene expression is a conseque nce of the chromosomal location and/or the nature of the primary trans gene integration event.