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. 2007 Feb 15;85(3):525-35.
doi: 10.1002/jnr.21139.

Mouse and rat BDNF gene structure and expression revisited

Tamara Aid  1 , Anna Kazantseva, Marko Piirsoo, Kaia Palm, Tõnis Timmusk
Affiliations

Mouse and rat BDNF gene structure and expression revisited

Tamara Aid et al. J Neurosci Res. .

Abstract

Brain-derived neurotrophic factor (BDNF) has important functions in the development of the nervous system and in brain plasticity-related processes such as memory, learning, and drug addiction. Despite the fact that the function and regulation of rodent BDNF gene expression have received close attention during the last decade, knowledge of the structural organization of mouse and rat BDNF gene has remained incomplete. We have identified and characterized several mouse and rat BDNF transcripts containing novel 5' untranslated exons and introduced a new numbering system for mouse and rat BDNF exons. According to our results both mouse and rat BDNF gene consist of eight 5' untranslated exons and one protein coding 3' exon. Transcription of the gene results in BDNF transcripts containing one of the eight 5' exons spliced to the protein coding exon and in a transcript containing only 5' extended protein coding exon. We also report the distinct tissue-specific expression profiles of each of the mouse and rat 5' exon-specific transcripts in different brain regions and nonneural tissues. In addition, we show that kainic acid-induced seizures that lead to changes in cellular Ca(2+) levels as well as inhibition of DNA methylation and histone deacetylation contribute to the differential regulation of the expression of BDNF transcripts. Finally, we confirm that mouse and rat BDNF gene loci do not encode antisense mRNA transcripts, suggesting that mechanisms of regulation for rodent and human BDNF genes differ substantially.

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Figures

Fig. 1
Fig. 1
Exon/intron structure and alternative transcripts of mouse and rat BDNF genes. A: Rat BDNF gene structure as described by Timmusk et al. (1993). Exons are shown as boxes and introns are shown as lines. B: The new arrangement of exons and introns of mouse and rat BDNF genes as determined by analyzing genomic and mRNA sequence data using bioinformatics, 5′ RACE, and RT-PCR. The schematic representation of BDNF transcripts in relation to the gene is shown below the gene structure. Protein coding regions are shown as solid boxes and untranslated regions are shown as open boxes. Each of the eight 5′ untranslated exons is spliced to the common 3′ protein coding exon IX. In addition, transcription can be initiated in the intron before the protein coding exon, which results in IXA transcripts containing 5′ extended coding exon. Each transcription unit may use one of the two alternative polyadenylation signals in the 3′ exon (arrows). For exon II, three different transcript variants, IIA, IIB, and IIC, are generated as a result of using alternative splice-donor sites in exon II (arrows marked A, B, and C).
Fig. 2
Fig. 2
Expression analysis of mouse and rat BDNF mRNAs. Semiquantitive RT-PCR analysis of tissue-specific expression of mouse (A) and rat (B) BDNF transcripts and control HPRT mRNA was performed in developing and adult brain and in peripheral organs. E, embryonic day; P, postnatal day.
Fig. 3
Fig. 3
Identification of the transcription start sites for BDNF new exon III, V, VII, VIII, and IXA mRNAs in rat. 5′ Rapid amplification of cDNA ends (5′ RACE) was performed to determine the transcription start sites for novel BDNF transcripts. Major transcription initiation sites (short arrows) are located at 152 bp and 230 bp for exon III (arrows marked A and B), at 81 bp for exon V and at 277 bp and 286 bp for exon VIII (arrows marked A and B) upstream of the 3′ end of the respective exon and at 476 bp and 363 bp upstream of the major splice acceptor site of the coding exon (asterisk) for exon IXA. For exon VII, the 5′end of the longest EST is shown as a putative transcription initiation site, because 5′ RACE did not result in any specific products as a result of very low levels of exon VII transcripts. Exon sequences are in boldface; intron sequences are in lowercase letters. The locations of primers that were used in 5′ RACE are indicated with long arrows.
Fig. 4
Fig. 4
Differential regulation of BDNF gene expression by DNA methylation and histone deacetylation. The role of DNA methylation in transcriptional activity of BDNF promoters was investigated by treating rat C6 glioma and mouse Neuro2A neuroblastoma cells with 1 μM 5-Aza-deoxycytidine (5AzadC) for 48 hr. The effects of inhibition of histone deacetylation was studied by treating Neuro2A and C6 cells with 300 nM trichostatin A (TSA) for 48 hr. Muscarinic acetylcholine receptor M4 gene and constitutive hypoxanthine-phosphoribosyltransferase (HPRT) gene were used as reference genes.
Fig. 5
Fig. 5
Activity-dependent regulation of BDNF exon-specific mRNAs in rat hippocampus by kainic acid-induced seizures. The effect of kainate-induced seizures on the expression of different BDNF transcripts in the hippocampus of adult rat brain was examined. Adult rats were injected subcutaneously with kainic acid (8 mg per kg body weight) and sacrificed 1, 3, 6, 12, and 24 hr posttreatment. Total RNA was extracted, and semiquantitative RT-PCR was performed. Untreated rat hippocampus RNA was used as a control.
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References

    1. Ballas N, Mandel G. The many faces of REST oversee epigenetic programming of neuronal genes. Curr Opin Neurobiol. 2005;15:500–506. - PubMed
    1. Ballas N, Grunseich C, Lu DD, Speh JC, Mandel G. REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell. 2005;121:645–657. - PubMed
    1. Baranova A, Hammarsund M, Ivanov D, Skoblov M, Sangfelt O, Corcoran M, Borodina T, Makeeva N, Pestova A, Tyazhelova T, et al. Distinct organization of the candidate tumor suppressor gene RFP2 in human and mouse: multiple mRNA isoforms in both species- and human-specific antisense transcript RFP2OS. Gene. 2003;321:103–112. - PubMed
    1. Bibel M, Barde YA. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 2000;14:2919–2937. - PubMed
    1. Binder DK. The role of BDNF in epilepsy and other diseases of the mature nervous system. Adv Exp Med Biol. 2004;548:34–56. - PubMed

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