TISSUE-SPECIFIC EXPRESSION AND CHROMOSOMAL LOCALIZATION OF THE ALPHA-SUBUNIT OF MOUSE MEPRIN-A

Meprins, membrane-bound oligomeric metalloendopeptidases, contain alph a and/or beta subunits. Their activities have been found in the mouse and rat kidney. The cloned cDNA for the mouse alpha subunit of meprin A (EC 3.4.24.18) was used here to survey mRNA expression in kidney of different mouse strains and in various tissues of mice and rats. A sin gle message of 3.6 kilobases was found in kidney of random bred (ICR) and inbred mice (C57BL/6, DBA/2) that contain high meprin A activity a nd in Sprague-Dawley rat kidney. The alpha subunit message was undetec table in the kidney of C3H/He and CBA mice, inbred strains that do not express meprin A activity. Therefore, meprin A activity in the kidney of mouse strains correlates with the amount of alpha subunit mRNA pre sent. The 3.6-kilobase mRNA meprin alpha subunit message was also dete cted in the small intestine of the rat but not in mice. No message was detected in brain, heart, skeletal muscle, liver, lung, or spleen of mice or rats. Polymerase chain reaction amplification or Southern blot analysis of genomic DNA revealed that the gene for the alpha subunit is present in all mouse strains as well as in human, monkey, rat, mous e, dog, cow, rabbit, and chicken, but it was not detected in yeast. Th ere is one gene copy present in the mouse genome. The gene was localiz ed to mouse chromosome 17 centromeric to the major histocompatibility complex (H-2) by the interspecific backcrossing method. The localizati on of this allele to Mep-1, the gene previously found to regulate the expression of meprin A activity in mice, supports the proposal that Me p-1 is the structural gene for the alpha subunit.