EXPRESSION OF MESSENGER-RNAS FOR LYSYL OXIDASE AND TYPE-III PROCOLLAGEN IN CULTURED FIBROBLASTS FROM PATIENTS WITH THE MENKES AND OCCIPITALHORN SYNDROMES AS DETERMINED BY QUANTITATIVE POLYMERASE CHAIN-REACTION

The Menkes syndrome and the occipital horn syndrome are two X-linked r ecessively inherited disorders characterized by abnormalities in coppe r metabolism, These abnormalities are associated with a reduction in t he activity of lysyl oxidase (EC 1.4.3.13), an extracellular copper en zyme that initiates the crosslinking of collagens and elastin. We repo rt here that the amount of lysyl oxidase mRNA, as studied by Northern blotting, and the number of lysyl oxidase mRNA molecules per picogram of RNA, as determined by a quantitative PCR method, were decreased in three cultured skin fibroblast lines from patients with the Menkes syn drome and two from patients with the occipital horn syndrome compared with four control cell lines. The decreased lysyl oxidase activity fou nd in these disorders thus appears to be at least in part due to a pre translational mechanism. No decrease was found in the number of the be ta-actin mRNA molecules in the Menkes cell lines, but rather a slight increase, whereas a decrease was found in these molecules in the occip ital horn cell lines. An additional abnormality found in the Menkes ce ll lines was a significant increase in the number of mRNA molecules fo r type III procollagen in two of the three cell lines investigated, Th e present and previous data indicate that the Menkes syndrome may invo lve several abnormalities in the expression of genes for connective ti ssue proteins. (C) 1996 Academic Press, Inc.