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Mesothelin is not required for normal mouse development or reproduction
1Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA.
Abstract:
Mesothelin is a glycosylphosphatidylinositol-linked glycoprotein highly expressed in mesothelial cells, mesotheliomas, and ovarian cancer, but the biological function(s) of the protein is not known. We have analyzed the expression of the mouse mesothelin gene in different developmental stages and in various adult tissues by Northern hybridization. The 2.5-kb mesothelin transcript was detected in the mRNA of E 7.0, E 15.0, and E 17.0 stages of mouse development. In adult tissues the mesothelin gene was expressed in lung, heart, spleen, liver, kidney, and testis. To directly assess the function of the mesothelin in vivo, we generated mutant mice in which the mesothelin gene was inactivated by replacing it with the neomycin resistance gene. In homozygous mutant mice neither mesothelin mRNA nor the protein product was detected. Null mutant mice were obtained in accordance with Mendelian laws, and both males and females produced offspring normally. No anatomical or histological abnormalities were detected in any tissues where mesothelin was reportedly expressed in wild-type mice. Our results demonstrate that mesothelin function is not essential for growth or reproduction in mice.
Insights
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.
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.
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.