Characterization of astrocyte-specific conditional knockouts

被引:78
作者
Casper, Kristen B. [1 ]
Jones, Kristin [1 ]
McCarthy, Ken D. [1 ]
机构
[1] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA
关键词
CreERT2; GFAP; tamoxifen; astrocyte; Cre recombinase; inducible gene recombination; doxycyline;
D O I
10.1002/dvg.20287
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Conditional gene knockouts are a very powerful tool for elucidating gene function in animal physiology and behavior. To obtain cell-specific knockouts, a promoter is utilized that drives expression of Cre recombinase specifically to the cell population of interest. We describe several transgenic lines of mice that were created in an attempt to obtain astrocyte-specific gene recombination. A 2 kb fragment from the human glial fibrillary acidic protein promoter is utilized to drive expression of inducible Cre recombinase, with both the Tet-Off and tamoxifen responsive systems. We show data obtained from crosses with two Cre reporter lines, ROSA26R and an astrocyte Cre reporter created in our laboratory, to assess the cell specificity of gene recombination. Additionally, our system is shown to successfully recombine a floxed Connexin43 locus, although recombination is not as extensive as seen in crosses with reporter lines.
引用
收藏
页码:292 / 299
页数:8
相关论文
共 45 条
[21]   Endothelial cell-specific knockout of connexin 43 causes hypotension and bradycardia in mice [J].
Liao, Y ;
Day, KH ;
Damon, DN ;
Duling, BR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (17) :9989-9994
[22]   Interferon-γ induced medulloblastoma in the developing cerebellum [J].
Lin, WS ;
Kemper, A ;
McCarthy, KD ;
Pytel, P ;
Wang, JP ;
Campbell, IL ;
Utset, MF ;
Popko, B .
JOURNAL OF NEUROSCIENCE, 2004, 24 (45) :10074-10083
[23]   Timing the doxycycline yields different patterns of genomic recombination in brain neurons with a new inducible Cre transgene [J].
Lindeberg, J ;
Mattsson, R ;
Ebendal, T .
JOURNAL OF NEUROSCIENCE RESEARCH, 2002, 68 (02) :248-253
[24]   Neuronal or glial progeny:: Regional differences in radial glia fate [J].
Malatesta, P ;
Hack, MA ;
Hartfuss, E ;
Kettenmann, H ;
Klinkert, W ;
Kirchhoff, F ;
Götz, M .
NEURON, 2003, 37 (05) :751-764
[25]   Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells [J].
Masahira, Noritaka ;
Takebayashi, Hirohide ;
Ono, Katsuhiko ;
Watanabe, Keisuke ;
Ding, Lei ;
Furusho, Miki ;
Ogawa, Yasuhiro ;
Nabeshima, Yo-ichi ;
Alvarez-Buylla, Arturo ;
Shimizu, Keiji ;
Ikenaka, Kazuhiro .
DEVELOPMENTAL BIOLOGY, 2006, 293 (02) :358-369
[26]   Site- and time-specific gene targeting in the mouse [J].
Metzger, D ;
Chambon, P .
METHODS, 2001, 24 (01) :71-80
[27]   Inducible gene deletion in astroglia and radial glia -: A valuable tool for functional and lineage analysis [J].
Mori, Tetsuji ;
Tanaka, Kohichi ;
Buffo, Annalisa ;
Wurst, Wolfgang ;
Kuehn, Ralf ;
Goetz, Magdalena .
GLIA, 2006, 54 (01) :21-34
[28]   Connexins and gap junctions of astrocytes and oligodendrocytes in the CNS [J].
Nagy, JI ;
Rash, JE .
BRAIN RESEARCH REVIEWS, 2000, 32 (01) :29-44
[29]   The fate of neural progenitor cells expressing astrocytic and radial glial markers in the postnatal rat dentate gyrus [J].
Namba, T ;
Mochizuki, H ;
Onodera, M ;
Mizuno, Y ;
Namiki, H ;
Seki, T .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2005, 22 (08) :1928-1941
[30]   Astrocytic purinergic signaling coordinates synaptic networks [J].
Pascual, O ;
Casper, KB ;
Kubera, C ;
Zhang, J ;
Revilla-Sanchez, R ;
Sul, JY ;
Takano, H ;
Moss, SJ ;
McCarthy, K ;
Haydon, PG .
SCIENCE, 2005, 310 (5745) :113-116