BAC Transgenic Mice Reveal Distal Cis-Regulatory Elements Governing BDNF Gene Expression

نویسندگان

  • Indrek Koppel
  • Tamara Aid-Pavlidis
  • Kaur Jaanson
  • Mari Sepp
  • Kaia Palm
  • Tõnis Timmusk
چکیده

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of neurotrophic factors, has important functions in the peripheral and central nervous system of vertebrates. We have generated bacterial artificial chromosome (BAC) transgenic mice harboring 207 kb of the rat BDNF (rBDNF) locus containing the gene, 13 kb of genomic sequences upstream of BDNF exon I, and 144 kb downstream of protein encoding exon IX, in which protein coding region was replaced with the lacZ reporter gene. This BDNF-BAC drove transgene expression in the brain, heart, and lung, recapitulating endogenous BDNF expression to a larger extent than shorter rat BDNF transgenes employed previously. Moreover, kainic acid induced the expression of the transgenic BDNF mRNA in the cerebral cortex and hippocampus through preferential activation of promoters I and IV, thus recapitulating neuronal activity-dependent transcription of the endogenous BDNF gene.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Expression of human smooth muscle calponin in transgenic mice revealed with a bacterial artificial chromosome.

Defining regulatory elements governing cell-restricted gene expression can be difficult because cis-elements may reside tens of kilobases away from start site(s) of transcription. Artificial chromosomes, which harbor hundreds of kilobases of genomic DNA, preserve a large sequence landscape containing most, if not all, regulatory elements controlling the expression of a particular gene. Here, we...

متن کامل

Selectable Marker Gene Removal and Expression of Transgene by Inducible Promoter Containing FFDD Cis-Acting elements in Transgenic plants

Abstract Background: Selectable marker gene (SMG) systems are critical for generation of transgenic crops. Transgenic crop production Background: Selectable marker gene (SMG) systems are critical for generation of transgenic crops. Transgenic crop production without using SMG is not economically feasible. However, SMGs are non-essential once an intact transgenic plant has been established. Eli...

متن کامل

Recombineering of BAC DNA for the Generation of Transgenic Mice

The use of BAC plasmids for transgenic gene expression is also gaining popularity over traditional proximal promoter driven transgene expression because the BAC typically contain most, if not all, of the important regulatory elements required to recapitulate endogenous gene expression (Giraldo and Montoliu 2001). Maintaining the coding sequence within its regulatory locus insulates the transgen...

متن کامل

Harnessing mobile genetic elements to explore gene regulation

Sequences that regulate expression of a gene in cis but are located at large distances along the DNA from the gene, as found with most developmentally regulated genes in higher vertebrates, are difficult to identify if those sequences are not conserved across species. Mutating suspected gene-regulatory sequences to alter expression then becomes a hit-or-miss affair. The relaxed specificity of t...

متن کامل

Evaluation of MYB93 and MAD8 Genes in Transgenic and Non-Transgenic Rice

Increasing drought tolerance, especially in rice, which is one of the most important crops in Asia, is necessary. Transcription factors are specific sequence DNA-binding proteins that are capable of activating or suppressing transcription. These proteins regulate gene expression levels by binding to cis regulatory elements in the promoter of target genes to control various biological processes ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 48  شماره 

صفحات  -

تاریخ انتشار 2010