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Pleiotropic effects of a null mutation in the c-fos proto-oncogene

R S Johnson1, B M Spiegelman, V Papaioannou

  • 1Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.

Cell
|November 13, 1992
PubMed

Insights

The c-fos proto-oncogene is crucial for development and function in multiple tissues. Homozygous mutants exhibit severe osteopetrosis and developmental defects but can survive to adulthood.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • The c-fos proto-oncogene plays a key role in cellular responses to external stimuli.
  • Understanding c-fos function is vital for comprehending developmental processes and disease.

Purpose of the Study:

  • To investigate the in vivo function of c-fos during embryonic development and postnatal life.
  • To characterize the phenotypic consequences of c-fos deficiency in mice.

Main Methods:

  • Generation of chimeric mice with targeted c-fos mutations using embryonic stem cells.
  • Germline transmission and analysis of homozygous c-fos mutant mice.
  • Phenotypic characterization including growth, skeletal development, and organ function.

Main Results:

  • Homozygous c-fos mutants display reduced placental and fetal weights, with high perinatal mortality.
  • Surviving mutants develop severe osteopetrosis, characterized by bone ossification and impaired tooth eruption.
  • Additional defects include delayed gametogenesis, lymphopenia, and altered behavior, yet many survive to adulthood.

Conclusions:

  • c-fos is essential for the proper development and function of specific tissues, not broadly required for cell growth.
  • Osteopetrosis and other developmental abnormalities highlight c-fos's critical role in skeletal and immune system development.
  • The study underscores the complex and tissue-specific functions of c-fos in mammalian development.

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