Deregulated c-fos expression interferes with normal bone development in transgenic mice

Abstract

Transgenic mice were generated expressing c-fos genes under the control of the human metallothionein promoter. Although high levels of c-fos messenger RNA were detectable in a variety of tissues, deregulated c-fos expression specifically interfered with normal bone development without inducing malignant tumours.

The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice

“…Together these results strongly support that the expression of the FUS-CHOP oncogene does not require further complementary genetic changes in order to transform the adipose target cell. The apparent single-step action of the FUS-CHOP contrasts with previous experience with transgenic mice bearing other oncogenes (Adams et al, 1985;Leder et al, 1986;Quaife et al, 1987;Ruther et al, 1987;Sinn et al, 1987). However, if one considers the combined e ects of FUS-CHOP on di erentiation and proliferation controls, it seems reasonable to think that the single chromosome abnormality that leads to the generation of this protein may be all that is needed for the liposarcoma target cells to become transformed.…”

Overexpression of fra-2 in transgenic mice perturbs normal eye development

“…In the case of c-fos, over-expression of the gene under the control of either the metallothionein (MT) promoter (Ruther et al, 1987) or the H2-K b promoter (Grigoriadis et al, 1993), combined with replacement of 3' UTR mRNAdestabilising sequences with a viral long terminal repeat (LTR) sequence, resulted in development of lesions on the long bones of the legs. The further development of these lesions into osteosarcomas was variable and may have depended upon the level of expression of the transgene.…”

Expression of c‐fos gene inhibits proteoglycan synthesis in transfected chondrocyte

“…The proto-oncogene c-fos is the cellular homologue of the v-fos which was originally obtained from the murine sarcoma virus [1,2]. Overexpression of c-fos in transgenic mice, carrying the exogenous mouse c-los gene under the control of the metallothionein promoter, deteriorated bone metabolism [3]; interfering with bone formation by inhibiting collagen synthesis in osteoblast [4] and enhancing osteoclast differentiation [5].…”