a- and p-adrenergic agonists (Schilling et al. 1991). Thus, activation of both 
the protein kinase A and protein kinase C pathways are efficiently coupled to 
expression of the fusion gene. The induction of c -fos and the fusion gene was 
both rapid and transient, but the fusion protein had a slightly greater half-life 
than endogenous Fos (Schilling et al. 1991). Therefore, it was concluded that 
this fusion gene, when tested in culture, behaved like endogenous fos and was 
appropriate for use in transgenic mice. 
Several lines of transgenic mice bearing the fos-lacZ transgene have been 
derived (Smeyne et al. 1992). Three areas of research have been performed 
to date and these are summarized here. 
Constitutive Sites of Fos-LacZ Expression 
In unstimulated mice, several tissues express the transgene constitutively. 
Such tissues include the skin, root sheath cells of the hair follicle, ossifying 
chondrocytes, and cells that give rise to the nail. This suggested that 
constitutive expression of the transgene (and c -fos) is associated with cells 
that are in terminal differentiation and are destined to die. Subsequently, 
this notion has been extended by the observation of constitutive transgene 
expression in other cells that exhibit programed cell death in vivo. What the 
relationship is between expression of c -fos and cell death is unknown at the 
present. 
Expression of Fos-LacZ in the Developing Nervous System 
During postnatal development, constitutive expression of fos-lacZ is readily 
detected in the nuclei of neurons in several regions of the CNS. Notable 
examples include, but are not limited to, mitral cells of the developing olfactory 
bulb, CA1 pyramidal neurons of the hippocampus, neurons in the cingulate 
cortex, and neurons within the parafascicular nucleus of the thalamus. Many 
of these sites are undergoing active synaptogenesis at the times that this 
expression is observed. However, it is unknown whether Fos is involved in, 
or responsive to, the synaptogenesis or plasticity of these neurons during this 
period. 
Induced Expression of Fos-LacZ in the Nervous System 
There are several sites of expression of the transgene in unstimulated mice 
during the daytime, such as the raphe and reticular formation (Smeyne et al. 
1992). It has been suggested that these sites of expression might be related to 
the state of arousal/sleep (Smeyne et al. 1992). However, following several 
forms of neural stimulation there ensues a rapid and transient induction of the 
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