Abstract:
:Fibroblast Growth Factors (FGFs) and their receptors (FGFRs) are widely expressed in the mature nervous system and are thought to mediate plasticity and repair. We report the generation of transgenic mice that can be induced to express a dominant-negative FGFR (dnFGFR) in select neuronal populations. We show that a modified Thy1 promoter [Vidal, M., Morris, R., Grosveld, F., and Spanopoulou, E. 1990. Tissue-specific control elements of the Thy-1 gene. EMBO J 9 833-840] can be used to drive widespread neuronal expression of the reverse tetracycline transactivator M2 (rtTA-M2 [Urlinger, S., Baron, U., Thellmann, M., Hasan, M.T., Bujard, H., and Hillen, W., 2000. Exploring the sequence space for tetracycline-dependent transcriptional activators: novel mutations yield expanded range and sensitivity. Proc. Natl. Acad. Sci. U. S. A. 97, 7963-7968]), which after stimulation with doxycycline induces co-expression of dnFGFR in mosaic subpopulations of rtTA-M2-positive forebrain neurons, but not in hindbrain and spinal cord rtTA-M2-positive neurons. Expression of dnFGFR did not cause overt neurodegeneration, but led to increased neuronal vulnerability: four days after a stab injury, cell death was marked in the hippocampus of dnFGFR-expressing animals when compared to controls. The nuclear morphology of dying CA1 pyramidal cells suggested an apoptotic mechanism of cell death. These observations demonstrate the importance of endogenous FGFs in the maintenance of the nervous system.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Eckenstein FP,McGovern T,Kern D,Deignan Jdoi
10.1016/j.expneurol.2005.12.020keywords:
subject
Has Abstractpub_date
2006-04-01 00:00:00pages
338-49issue
2eissn
0014-4886issn
1090-2430pii
S0014-4886(05)00452-8journal_volume
198pub_type
杂志文章abstract::The question of whether or not the development of dystrophic muscles is similar to that of normal muscles, prior to the manifestations of the symptoms of the disease, is investigated here. The developmental change in the activity of succinate dehydrogenase was therefore measured in individual fibers of prospectively d...
journal_title:Experimental neurology
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