Document Detail


Temporal control of gene recombination in astrocytes by transgenic expression of the tamoxifen-inducible DNA recombinase variant CreERT2.
MedLine Citation:
PMID:  16575885     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inducible gene modification using the Cre/loxP system provides a valuable tool for the analysis of gene function in the active animal. GFAP-Cre transgenic mice have been developed to achieve gene recombination in astrocytes, the most abundant cells of the central nervous system, with pivotal roles during brain function and pathology. Unfortunately, these mice displayed neuronal recombination as well, since the GFAP promoter is also active in embryonic radial glia, which possess a substantial neurogenic potential. To enable the temporal control of gene deletions in astrocytes only, we generated a transgenic mouse with expression of CreERT2, a fusion protein of the DNA recombinase Cre and a mutated ligand-binding domain of the estrogen receptor, under the control of the human GFAP promoter. In offspring originating from crossbreedings of GFAP-CreERT2-transgenic mice with various Cre-sensitive reporter mice, consecutive intraperitoneal injections of tamoxifen induced genomic recombination selectively in astrocytes of almost all brain regions. In Bergmann glia, which represent the main astroglial cell population of the cerebellum, virtually all cells showed successful gene recombination. When adult mice received cortical stab wound lesions, simultaneously given tamoxifen induced substantial recombination in reactive glia adjacent to the site of injury. These transgenic GFAP-CreERT2 mice will allow the functional analysis of loxP-modified genes in astroglia of the postnatal and adult brain.
Authors:
Petra G Hirrlinger; Anja Scheller; Christian Braun; Johannes Hirrlinger; Frank Kirchhoff
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Glia     Volume:  54     ISSN:  0894-1491     ISO Abbreviation:  Glia     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-05-25     Completed Date:  2006-07-27     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8806785     Medline TA:  Glia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11-20     Citation Subset:  IM    
Copyright Information:
Copyright 2005 Wiley-Liss, Inc.
Affiliation:
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents, Hormonal / pharmacology
Astrocytes / cytology,  metabolism*
Brain / cytology,  growth & development,  metabolism
Brain Injuries / genetics,  metabolism,  physiopathology
Cells, Cultured
Disease Models, Animal
Female
Gene Deletion
Gene Expression Regulation, Developmental / genetics*
Glial Fibrillary Acidic Protein / genetics
Gliosis / genetics,  metabolism,  physiopathology
Humans
Integrases / genetics*
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Promoter Regions, Genetic / genetics
Receptors, Estrogen / genetics*
Recombinant Fusion Proteins / biosynthesis,  genetics*
Recombination, Genetic / genetics*
Tamoxifen / pharmacology
Time Factors
Transgenes / genetics
Viral Proteins / genetics*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Hormonal; 0/Glial Fibrillary Acidic Protein; 0/Receptors, Estrogen; 0/Recombinant Fusion Proteins; 0/Viral Proteins; 10540-29-1/Tamoxifen; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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