Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Neuronal vulnerability in transgenic mice expressing an inducible dominant-negative FGF receptor. 1648 70

The Tetracycline (Tet)-controlled inducible system is the most widely used reversible system for transgene expression in mice with over 500 lines created to date. Although this system has been optimized over the years, it still has limitations such as residual transgene expression when turned off, referred to as leakiness. Here, we present a series of new Tet-OFF transgenic mice based on the second generation tetracycline-responsive transactivator system. The tTA-Advanced (tTA2(S)) is expressed under control of the neuron-specific Thy1.2 promoter (Thy-OFF), to regulate expression in the mouse brain. In addition, we generated a lacZ reporter line, utilizing the P tight Tet-responsive promoter (P(tight)-lacZ), to test our system. Two Thy-OFF transgenic lines displaying two distinct patterns of expression were selected. Oral doxycycline treatment of Thy-OFF/P tight-lacZ mice demonstrated tight transgene regulation with no leak expression. These new Thy-OFF mice are valuable for studies in a broad range of neurodegenerative diseases such as Alzheimer's disease and related forms of dementia, where control of transgene expression is critical to understanding mechanisms underlying the disease. Furthermore, P tight-lacZ reporter mice may be widely applicable.
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PMID:Inducible, tightly regulated and non-leaky neuronal gene expression in mice. 2421 94