The
Menkes syndrome and the
occipital horn syndrome are two X-linked recessively inherited disorders characterized by abnormalities in
copper metabolism. These abnormalities are associated with a reduction in the activity of
lysyl oxidase (EC 1.4.3.13), an extracellular
copper enzyme that initiates the crosslinking of
collagens and
elastin. We report 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 syndrome and two from patients with the
occipital horn syndrome compared with four control cell lines. The decreased
lysyl oxidase activity found in these disorders thus appears to be a least in part due to a pretranslational mechanism. No decrease was found in the number of the
beta-actin mRNA molecules in the Menkes cell lines, but rather a slight increase, whereas a decrease was found in these molecules in the occipital horn cell lines. An additional abnormality found in the Menkes cell lines was a significant increase in the number of
mRNA molecules for
type III procollagen in two of the three cell lines investigated. The present and previous data indicate that the
Menkes syndrome may involve several abnormalities in the expression of genes for connective tissue
proteins.