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Publication : Species-specific changes in regulatory elements of mouse haptoglobin genes.

First Author  Pajovic S Year  1994
Journal  J Biol Chem Volume  269
Issue  3 Pages  2215-24
PubMed ID  8294478 Mgi Jnum  J:16501
Mgi Id  MGI:64576 Doi  10.1016/s0021-9258(17)42156-9
Citation  Pajovic S, et al. (1994) Species-specific changes in regulatory elements of mouse haptoglobin genes. J Biol Chem 269(3):2215-24
abstractText  Although expression of the haptoglobin (HP) as an acute phase reactant is evolutionarily conserved among mammals, there are differences among species with regard to the hormones required for stimulation. Using primary hepatocyte cultures, we show that in Mus caroli, as in rat, IL-1 and IL-6 are stimulatory, whereas in M. domesticus, as in humans, IL-1 response is diminished. In vivo, an acute inflammatory process increases hepatic HP expression in both mouse species up to 30-fold but minimally affects the low level HP expression in the lung. To define the species-specific differences in regulation, we isolated the hormone-responsive elements of the HP gene from the Mus species, M. domesticus, M. caroli, and M. saxicola. Functional studies in transfected hepatoma cells revealed an exceptionally strong dexamethasone response for all three murine HP gene elements. The IL-6 response was less prominent than in rat or human. A modest response to IL-1 was observed in M. caroli and M. saxicola. A mouse-specific insertion of a polypurine sequence led to a binding site for the PEA3 transcription factor in the HP gene promoter of M. domesticus and M. saxicola, but not M. caroli. The specific regulatory effects of glucocorticoid receptor, C/EBP beta, and Ets proteins were documented by co-transfection.
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