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 and the advancement of drug development within the pharmaceutical industry. In this report we describe a method which improves the yield of phenotypically desirable transgenic founder mice resulting from each microinjection session and consequently reduces animal requirements for transgenic production. 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 similar levels of coat pigmentation. Furthermore, the presence of insulators leads to visually identical tissue distribution of pigmentation including skin, fur, eyes, points, and foot pads. The overall impact of insulators is to reduce the number of transgenic founders required in order to identity animals with an appropriate expression level and tissue distribution.