Bond J S, Beynon R J, Reckelhoff J F, David C S
Proc Natl Acad Sci U S A. 1984 Sep;81(17):5542-5. doi: 10.1073/pnas.81.17.5542.
Meprin, a glycoprotein with potent metalloendopeptidase activity, is an integral component of the brush border membrane of mouse kidney. Previously we reported that genealogically related inbred mouse strains (C3H and CBA) are markedly deficient in the activity of this enzyme. We report here that meprin deficiency is inherited as an autosomal recessive trait and that several other inbred strains also express low levels of meprin activity. All of the inbred strains deficient in meprin activity are of the H-2k haplotype; however, two strains of this haplotype (C58 and C57BR/cd) expressed normal levels of the proteinase. Congeneic and recombinant mouse strains were examined to determine whether the deficiency was linked to the H-2 complex. The gene controlling the activity of meprin (Mep-1) maps on chromosome 17 to the right of the D end of the major histocompatibility complex. The Mep-1 gene is closely linked to a gene that controls isoenzyme patterns of phosphoglycerate kinase (Pgk-2). This work represents the localization of a gene that determines the activity of an integral cellular endopeptidase in mammalian tissues. In addition, the Mep-1 gene is the only identified gene linked to the major histocompatibility complex that regulates a proteinase activity.
金属蛋白酶，一种具有强大金属内肽酶活性的糖蛋白，是小鼠肾脏刷状缘膜的一个组成部分。此前我们报道，具有谱系关系的近交系小鼠品系（C3H和CBA）这种酶的活性明显缺乏。我们在此报道，金属蛋白酶缺乏作为常染色体隐性性状遗传，并且其他几个近交系也表现出低水平的金属蛋白酶活性。所有缺乏金属蛋白酶活性的近交系均为H-2k单倍型；然而，该单倍型的两个品系（C58和C57BR/cd）蛋白酶表达水平正常。检测了同源和重组小鼠品系，以确定这种缺乏是否与H-2复合体相关。控制金属蛋白酶（Mep-1）活性的基因定位于17号染色体上主要组织相容性复合体D端右侧。Mep-1基因与控制磷酸甘油酸激酶（Pgk-2）同工酶模式的基因紧密连锁。这项工作代表了一个决定哺乳动物组织中完整细胞内肽酶活性的基因的定位。此外，Mep-1基因是唯一确定的与调节蛋白酶活性的主要组织相容性复合体相关的基因。
