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Related Experiment Videos

The copper transporter CTR1 provides an essential function in mammalian embryonic development.

Y M Kuo1, B Zhou, D Cosco

  • 1Departments of Medicine and Pediatrics and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 8, 2001
PubMed
Summary

The CTR1 protein is essential for copper uptake in mammals. Inactivating the CTR1 gene in mice causes embryonic lethality and reduced copper in adult brains, confirming its vital role.

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Area of Science:

  • Biochemistry
  • Developmental Biology
  • Genetics

Background:

  • Copper is an essential cofactor for numerous proteins in all organisms.
  • The human CTR1 (SLC31A1) gene encodes a high-affinity copper uptake protein.
  • CTR1's role in copper delivery to mammalian cells was previously hypothesized.

Purpose of the Study:

  • To test the hypothesis that CTR1 is required for copper delivery to mammalian cells.
  • To investigate the function of CTR1 in mammalian development and copper homeostasis.

Main Methods:

  • Targeted mutagenesis to inactivate the Ctr1 gene in mice.
  • Analysis of homozygous and heterozygous mutant embryos for developmental abnormalities.
  • Measurement of copper levels in the brains of heterozygous adult mice.

Related Experiment Videos

  • Study of Ctr1 gene expression patterns during mouse development and adulthood.

    • Main Results:

    • Homozygous Ctr1(-/-) embryos exhibit early embryonic lethality (E8.5) with severe developmental retardation and morphological abnormalities.
    • Heterozygous adult mice show approximately 50% reduction in brain copper levels compared to controls.
    • Histological analysis of mutant embryos revealed basement membrane defects and impaired collagen cross-linking due to lysyl oxidase deficiency.
    • Ubiquitous Ctr1 transcription was observed, with highest expression in choroid plexus, renal tubules, and connective tissues of the eye, ovary, and testes.

    Conclusions:

    • CTR1 is essential for copper uptake in mammalian cells.
    • CTR1 plays a critical role in embryonic development, likely through copper delivery to support cuproenzyme activity.
    • CTR1 is the primary route for copper entry into mammalian organs, including the brain.