Alternate 5' exons in the rat brain-derived neurotrophic factor gene: differential patterns of expression across brain regions.
Brain-derived neurotrophic factor (BDNF) enhances the survival of dopaminergic neurons and protects them from neurotoxins in vitro. This trophic factor might thus be of therapeutic value for the treatment of Parkinsonian syndromes. The rat BDNF gene consists of several upstream noncoding exons that are alternatively spliced to a common coding exon. To investigate BDNF 5' exons expressed in the adult rat brain, we subjected RNA from cerebellum to 5'-RACE analysis and compared the resulting clones to previously reported 5' exon sequences from rat brain and hippocampus. In addition to known 5' exons, we isolated a BDNF transcript with a novel 5' sequence representing yet another alternate upstream exon in this gene. Quantitative PCR analysis of BDNF mRNAs containing each of the five upstream exons indicated that each of the alternate transcripts is most abundant in the hippocampus, intermediate in the substantia nigra and cerebellum and least abundant in the striatum. However, the magnitude of these differences in expression varied considerably suggesting that BDNF gene transcription in the mature brain is regulated by alternate promoters that are differentially active across regions.
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
J F
JF
Bishop
G P
GP
Mueller
M M
MM
Mouradian
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor; D002531:Cerebellum / Q000378:metabolism; D003001:Cloning, Molecular; D003342:Corpus Striatum / Q000378:metabolism; D017931:DNA Primers; D005091:Exons; D006624:Hippocampus / Q000378:metabolism; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009928:Organ Specificity; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D014158:Transcription, Genetic
D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins