Divergent expression of alpha1-protease inhibitor genes in mouse and human.
The alpha1-protease inhibitor proteins of laboratory mice are homologous in sequence and function to human alpha1-antitrypsin and are encoded by a highly conserved multigene family comprised of five members. In humans, the inhibitor is expressed in liver and in macrophages and decreased expression or inhibitory activity is associated with a deficiency syndrome which can result in emphysema and liver disease in affected individuals. It has been proposed that macrophage expression may be an important component of the function of human alpha1-antitrypsin. Clearly, it is desirable to develop a mouse model of this deficiency syndrome, however, efforts to do this have been largely unsuccessful. In this paper, we report that aside from the issues of potentially redundant gene function, the mouse may not be a suitable animal for such studies, because there is no significant expression of murine alpha1-protease inhibitor in the macrophages of mice. This difference between the species appears to result from an absence of a functional macrophage-specific promoter in mice.
Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Campus Box 347, Boulder, CO 80309, USA.
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Tardiff
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Krauter
D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013577:Syndrome; D000515:alpha 1-Antitrypsin / Q000235:genetics* / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D000515:alpha 1-Antitrypsin; D004247:DNA