Bone and haematopoietic defects in mice lacking c-fos.
The proto-oncogene c-fos is the cellular homologue of v-fos originally isolated from murine osteosarcoma. Fos protein is a major component of the AP-1 transcription factor complex, which includes members of the jun family. Stable expression of c-fos in mice has been demonstrated in developing bones and teeth, haematopoietic cells, germ cells and in the central nervous system. It has been proposed that c-fos has an important role in signal transduction, cell proliferation and differentiation. We have previously demonstrated that overexpression of c-fos in transgenic and chimaeric mice specifically affects bone, cartilage and haematopoietic cell development. To understand better the function of c-fos in vivo, we used gene targeting in embryonic stem cells to generate cells and mice lacking c-fos. Here we report that heterozygous fos +/- mice appear normal, although females exhibit a distorted transmission frequency. All homozygous fos -/- mice are growth-retarded, develop osteopetrosis with deficiencies in bone remodelling and tooth eruption, and have altered haematopoiesis. These data define the c-Fos protein as an essential molecule for the development of specific cellular compartments.
Wang
Z Q
ZQ
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
Ovitt
C
C
Grigoriadis
A E
AE
Möhle-Steinlein
U
U
Rüther
U
U
Wagner
E F
EF
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D001846:Bone Development / Q000235:genetics; D001842:Bone and Bones / Q000002:abnormalities*; D005260:Female; D017353:Gene Deletion; D016762:Genes, fos / Q000235:genetics / Q000502:physiology*; D006410:Hematopoiesis / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010022:Osteopetrosis / Q000235:genetics / Q000473:pathology; D015183:Restriction Mapping; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D014078:Tooth Eruption / Q000235:genetics