A HUMAN (3.3-KB) HAPTOGLOBIN CAT TRANSGENE IS MODULATED IN LUNGS OF TRANSGENIC MICE BY INFLAMMATION

Four independent lines of transgenic mice were produced carrying integ rated copies of a chimeric gene composed of 3.3 kb of the human haptog lobin 5' regulatory region fused to the CAT (chloramphenicol acetyl tr ansferase) reporter gene. Although the endogenous mouse haptoglobin (H p) and human haptoglobin (HP) genes express mainly in liver and lung, expression of the human 3.3-kb HP-CAT transgene was not detected until after induction of inflammation and then only in lungs. The results i ndicated that the transgene maintained the regulatory DNA elements req uired for lung specific responsiveness to inflammation in vivo but lac ked the DNA sequence required for robust expression in liver. The DNA sequence(s) responsible for the normally high level of HP expression i n liver either reside outside the 3.3-kb regulatory region of the HP c himeric gene or this region contains a suppressor sequence affecting t issue specific expression in the liver. (C) 1995 Academic Press, Inc.