Chicken beta-globin 5 ' HS4 insulators function to reduce variability in transgenic founder mice

Transgenic mice and rats play a vital role in the study of human diseases a nd the advancement of drug development within the pharmaceutical industry. In this report we describe a method which improves the yield of phenotypica lly desirable transgenic founder mice resulting from each microinjection se ssion and consequently reduces animal requirements for transgenic productio n. We have shown that by flanking a tyrosinase minigene with tandem copies of the chicken beta-globin 5'HS4 insulator there is a significant reduction in variability between transgenic lines, with resulting mice exhibiting si milar levels of coat pigmentation, Furthermore, the presence of insulators leads to visually identical tissue distribution of pigmentation including s kin, fur, eyes, points, and foot pads. The overall impact of insulators is to reduce the number of transgenic founders required in order to identity a nimals with an appropriate expression level and tissue distribution. (C) 20 00 Academic Press.