Lw. Lee et al., Essential role for mammalian copper transporter Ctr1 in copper homeostasisand embryonic development, P NAS US, 98(12), 2001, pp. 6842-6847
Citations number
46
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
The trace metal copper (Cu) plays an essential role in biology as a cofacto
r for many enzymes that include Cu, Zn superoxide dismutase, cytochrome oxi
dase. ceruloplasmin, lysyl oxidase, and dopamine beta -hydroxyiase, Consequ
ently, Cu transport at the cell surface and the delivery of Cu to intracell
ular compartments are critical events for a wide variety of biological proc
esses. The components that orchestrate intracellular Cu trafficking and the
ir roles in Cu homeostasis have been elucidated by the studies of model mic
roorganisms and by the characterizations of molecular basis of Cu-related g
enetic diseases, including Menkes disease and Wilson disease. However, litt
le is known about the mechanisms for Cu uptake at the plasma membrane and t
he consequences of defects in this process in mammals. Here, we show that t
he mouse Ctr1 gene encodes a component of the Cu transport machinery and th
at mice heterozygous for Ctr1 exhibit tissue-specific defects in copper acc
umulation and in the activities of copper-dependent enzymes. Mice completel
y deficient for Ctr1 exhibit profound growth and developmental defects and
die in utero in mid-gestation. These results demonstrate a crucial role for
Cu acquisition through the Ctr1 transporter for mammalian Cu homeostasis a
nd embryonic development.