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Next Article 
Volume 17, Number 22,
Issue of November 15, 1997
pp. 8657-8666
Cloning and Characterization of Murine Glial Cell-Derived
Neurotrophic Factor Inducible Transcription Factor (MGIF)
Received March 19, 1997; revised Aug. 21, 1997; accepted Aug. 25, 1997.
Shunsuke Yajima1,
Claas-Hinrich Lammers1,
Sang-Hyeon Lee1,
Yoshinobu Hara2,
Keiko Mizuno3, and
M. Maral Mouradian1
1 Genetic Pharmacology Unit, Experimental Therapeutics
Branch, National Institute of Neurological Diseases and Stroke,
2 Laboratory of Biochemical Genetics, National Heart, Lung,
and Blood Institute, and 3 Laboratory of Developmental
Neurobiology, National Institute of Child Health and Human Development,
Bethesda, Maryland 20892
The potent neurotrophic factor glial cell-derived neurotrophic
factor (GDNF) is a distant member of the transforming growth factor-
(TGF-) superfamily of proteins. We report a transcription factor
that is the first nuclear protein known to be induced by GDNF, thus
designated murine GDNF inducible factor (mGIF). The cDNA was cloned in
the course of investigating transcription factors that bind to Sp1
consensus sequences, using the in situ filter detection
method, and it was found to encode a protein having the same
C2-H2 zinc finger motif as Sp1. Sequence
analysis indicated that mGIF is homologous to the human TGF-
inducible early gene (TIEG) and human early growth response gene-
(EGR-). mGIF is widely distributed in the adult mouse with high mRNA
levels in kidney, lung, brain, liver, heart, and testis. In the adult
brain, mGIF is abundantly expressed in hippocampus, cerebral cortex, cerebellum, and amygdala with lower amounts in striatum, nucleus accumbens, olfactory tubercle, thalamus, and substantia nigra. During
development, mGIF mRNA also has a wide distribution, including in
cerebral cortex, cerebellar primordium, kidney, intestine, liver, and
lung. GDNF induces the expression of mGIF rapidly and transiently both
in a neuroblastoma cell line and in primary cultures of rat embryonic
cortical neurons. Co-transfection of the Drosophila SL2
cells using mGIF expression plasmid and reporter constructs having Sp1
binding sites indicated that mGIF represses transcription from a
TATA-containing as well as from a TATA-less promoter. These observations suggest that the zinc finger transcription factor mGIF
could be important in mediating some of the biological effects of
GDNF.
Key words:
glial cell-derived neurotrophic factor (GDNF);
zinc
finger;
Sp1;
transcription;
cloning;
transforming growth factor-
(TGF-)
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