EXPRESSION AND DISTRIBUTION OF MEPRIN PROTEASE SUBUNITS IN MOUSE INTESTINE

Meprins, zinc metalloendopeptidases of kidney and intestinal brush bor der membranes, are composed of differing ratios of alpha and beta subu nits. Previous work. indicated that the beta subunit was expressed in kidney and intestine of all mouse strains, but that the alpha subunit was only expressed in kidney of random-bred and some inbred strains an d not in mouse intestine. The work herein, however, reports that low l evels of meprin alpha subunit mRNA and protein are detectable in mouse intestine and are present in increasing concentrations from the duode num to the ileum. In ICR mice, the duodenum expressed less than 1% of the meprin alpha mRNA (mu g/g tissue) relative to kidney, the ileum ap proximately 20%. The large intestine contained approximately 10% of th e message found in kidney. An inbred mouse strain, C3H/He, found previ ously to contain only meprin beta subunits in kidney aad intestine, di splayed very low levels of meprin alpha mRNA (approximately 1% of that in ICR kidney) in both the kidney and intestine. Intestinal meprin be ta mRNA in ICR and C3H/He mice, by contrast, was expressed at similar levels to that found in kidney, and for both strains there was an incr ease (two- to threefold) in the beta message in the ileum relative to duodenum or jejunum. In general, the pattern of the meprin alpha prote in along the intestine was similar to that of a mRNA, and activity and response of intestinal meprin A to inhibitors were typical of the enz yme isolated from kidney. These data indicate that meprin a can be det ected in mouse small and large intestine and that expression is not on ly tissue- and strain-specific but also longitudinally variable in int estine. The expression pattern for both alpha and beta subunits indica tes an ileal function for the meprins. (C) 1996 Academic Press, Inc.