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Mesothelin is not required for normal mouse development or reproduction.

T K Bera1, I Pastan

  • 1Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA.

Molecular and Cellular Biology
|March 25, 2000
PubMed
Summary

The biological function of mesothelin, a protein found in mesothelial cells and cancers, is unknown. Studies show mesothelin is not essential for mouse growth or reproduction.

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Area of Science:

  • Biochemistry
  • Developmental Biology
  • Genetics

Background:

  • Mesothelin is a glycosylphosphatidylinositol-linked glycoprotein.
  • It is highly expressed in mesothelial cells, mesotheliomas, and ovarian cancer.
  • The biological function of mesothelin remains largely unknown.

Purpose of the Study:

  • To analyze the expression of the mouse mesothelin gene during development and in adult tissues.
  • To directly assess the in vivo function of mesothelin by generating a knockout mouse model.

Main Methods:

  • Northern hybridization was used to analyze mesothelin gene expression in various developmental stages and adult tissues.
  • Gene targeting was employed to create mesothelin-inactivated (null mutant) mice by replacing the gene with a neomycin resistance gene.

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Main Results:

  • Mesothelin transcripts were detected during mouse embryonic development (E 7.0, E 15.0, E 17.0).
  • The mesothelin gene was expressed in adult mouse tissues including lung, heart, spleen, liver, kidney, and testis.
  • Homozygous mutant mice lacking mesothelin showed no detectable mRNA or protein.
  • Null mutant mice were viable, fertile, and exhibited no anatomical or histological abnormalities.

Conclusions:

  • Mesothelin expression is present during mouse development and in various adult tissues.
  • Mesothelin function is not essential for normal growth, reproduction, or tissue integrity in mice.