Metallothionein Messenger RNA Levels in the Macular Mutant Mouse: An Animal Model of Menkes’ Kinky-Hair Disease

Abstract

Levels of metallothionein-1 (MT-1) messenger RNA (mRNA) in various tissues from normal and macular mutant mice at different stages of development (17 days of gestation, 1-, 3-, 7- and 14-day-old) were determined by Northern blot analysis. Renal MT-1 mRNA levels in mutant mice were slightly elevated at 3 stages compared to normal mice, with the exception of mutant fetus and 3-day-old mutant mice. Intestinal MT-1 mRNA levels in mutant mice were elevated at 3 stages compared to normal mice with the exception of mutant fetus and 3-day-old mutant mice. Hepatic MT-1 mRNA levels in mutant fetus and 1-day-old mutant mice were approximately the same compared to normal mice. In 3- and 7-day-old mutant mice, hepatic MT-1 mRNA levels were depressed and in 14-day-old mutant mice, they were increased compared to normal mice. Brain MT-1 mRNA could not be detected in normal and mutant mice at the 4 stages with the exception of 14-day-old mice. MT-1 mRNA in 14-day-old mice was detected and the level of that in mutant mice was slightly elevated compared to normal mice. After injection of Cu, MT-1 mRNA levels in kidney, liver and intestine were determined. The injection of Cu increased the level of MT-1 mRNA in the tissues of normal and mutant mice compared to control (saline-injected) mice. Significant differences in MT-1 mRNA levels in the tissues of both Cu-injected mice were not observed.

α-lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance

“…Inactivation of ATP7A results in the entrapment of dietary Cu in enterocytes, impaired Cu export from the intestine to the rest of the body, and systemic Cu deficit. Despite Cu deficiency, MNK patients exhibit paradoxical Cu accumulation in kidneys ( 9 , 10 ), which worsens with Cu supplementation therapy and complicates patients’ treatment. In another disorder of Cu homeostasis, Wilson disease (WD), mutations in the Cu(I) transporter ATP7B disrupt Cu export from the liver, disabling the major route of Cu removal from the body.…”