Genetically-targeted and conditionally-regulated ablation of astroglial cells in the central, enteric and peripheral nervous systems in adult transgenic mice1Published on the World Wide Web on 7 June 1999.1

Sofroniew, Michael V.; Bush, Toby G.; Blumauer, Natalie; Kruger, Lawrence; Mucke, Lennart; Johnson, Martin H.

doi:10.1016/s0006-8993(99)01639-x

Cited by 45 publications

(34 citation statements)

References 30 publications

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“…Administration of gancyclovir to such mice in conjunction with neurotrauma led to the elimination of dividing GFAP-positive cells that predominantly constitute the dividing subpopulation of reactive astrocytes. The results obtained from this mouse model showed that the dividing subpopulation of reactive astrocytes has a positive role in the acute repair process limiting the extent of neurodegeneration and allowing the repair of the blood-brain barrier, and suggested that astrocyte activation and reactive astrogliosis are important for the acute response after brain or spinal cord trauma (36,71,222). The above transgenic mouse model also helped to establish that most, if not all, adult mouse neural stem/ progenitor cells (NSC/NPSs) at least transiently express GFAP (75,137).…”

Section: Experimental Manipulation Of Reactive Astrogliosis In Cnmentioning

confidence: 89%

Astrocyte Reactivity and Reactive Astrogliosis: Costs and Benefits

Pekny

Pekna

2014

Physiological Reviews

701

576

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Astrocytes are the most abundant cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, as well as fulfill a wide range of other homeostasis maintaining functions. During the past two decades, astrocytes emerged also as increasingly important regulators of neuronal functions including the generation of new nerve cells and structural as well as functional synapse remodeling. Reactive gliosis or reactive astrogliosis is a term coined for the morphological and functional changes seen in astroglial cells/astrocytes responding to CNS injury and other neurological diseases. Whereas this defensive reaction of astrocytes is conceivably aimed at handling the acute stress, limiting tissue damage, and restoring homeostasis, it may also inhibit adaptive neural plasticity mechanisms underlying recovery of function. Understanding the multifaceted roles of astrocytes in the healthy and diseased CNS will undoubtedly contribute to the development of treatment strategies that will, in a context-dependent manner and at appropriate time points, modulate reactive astrogliosis to promote brain repair and reduce the neurological impairment.

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Section: Experimental Manipulation Of Reactive Astrogliosis In Cnmentioning

confidence: 89%

Astrocyte Reactivity and Reactive Astrogliosis: Costs and Benefits

Pekny

Pekna

2014

Physiological Reviews

701

576

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“…The cell-specific expression of the HSV-1 TK is a well established and a highly efficient technique to achieve conditional and selective ablation of specific cell types in transgenic mice (Salomon et al, 1995;Sofroniew et al, 1999). Expression of HSV-1 TK by the CD11b promoter enables control of the moment and duration of ablation of proliferating microglial cells as ablation can be regulated by administration of ganciclovir.…”

Section: Discussionmentioning

confidence: 99%

Mouse model for ablation of proliferating microgliain acute CNS injuries

Gowing

Vallières

Julien

2005

Glia

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Activation of microglia, the primary immune effectors of the CNS and proinflammatory signaling, is a hallmark of brain damage. However, it remains controversial whether microglial cells have beneficial or detrimental functions in various neuropathological conditions. We report the generation of transgenic mice that express a mutant form of herpes simplex virus type 1 thymidine kinase (HSV-1 TK(mt-30)) driven by the myeloid-specific CD11b promoter. Using two paradigms of nervous system damage, hypoglossal nerve axotomy, and cortical stab injury, we show that specific ablation of proliferating microglia in CD11b-TK(mt-30) mice can be achieved by administration of ganciclovir. For example, after hypoglossal nerve injury, a 75% reduction in proliferating microglial cells was observed at the site of injury. The CD11b-TK(mt-30) transgenic mouse should provide a valuable tool for studying the role of microglia in CNS damage and repair.

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“…The mGFAP-TK transgene is presumed to be active in enteric glia, as these cells are ablated by treatment with ganciclovir (77,78); one of six gfa2-lacZ lines (gfa2-nlac1, A.M., unpublished observations) was also found to express in enteric glia, as well as a hGFAP-hemagglutin transgene (31). Rio et al (62) found that both the gfa2-nlac1 and gfa2-GFP transgenic mice express in support cells and other epithelial cells of the inner ear, and Hainfellner et al (59) deduced the expression of a mGFAP-v-src transgene in fibroblasts, Schwann cells and enteric glia based on the development of tumors in these tissues.…”

Section: Non-cns Expression Of Gfap Transgenesmentioning

confidence: 99%

Expression Specificity of GFAP Transgenes

Lee

et al. 2004

Neurochem Res

106

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Glial fibrillary acidic protein (GFAP) is an intermediate filament protein found predominantly in astrocytes. This specificity has recommended the GFAP gene promoter for targeting transgene expression to astrocytes. Although both we [Brenner et al. J. Neurosci. 14:1030-1037, (1994)] and others [Mucke et al. New Biol. 3:465-474, (1991)] have reported astrocyte specificity for GFAP promoters, we demonstrate here that these DNA sequences can also direct activity in neurons. The pattern of neuronal activity varied with both the nature of the expressed sequence and the transgene insertion site. Specifically, neuronal expression was very high for a protective protein/cathepsin A minigene, moderate for lacZ and undetectable for GFP. These findings, coupled with a survey of the literature, recommend that investigators using GFAP-driven transgenes verify specificity for each line studied, using a detection system whose sensitivity is sufficient to detect a compromising level of misexpression.

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Genetically-targeted and conditionally-regulated ablation of astroglial cells in the central, enteric and peripheral nervous systems in adult transgenic mice1Published on the World Wide Web on 7 June 1999.1

Cited by 45 publications

References 30 publications

Astrocyte Reactivity and Reactive Astrogliosis: Costs and Benefits

Astrocyte Reactivity and Reactive Astrogliosis: Costs and Benefits

Mouse model for ablation of proliferating microgliain acute CNS injuries

Expression Specificity of GFAP Transgenes

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