Dataset Information

BAC transgenic mice reveal distal cis-regulatory elements governing BDNF gene expression.

ABSTRACT: 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.

SUBMITTER: Koppel I

PROVIDER: S-EPMC2978326 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

BAC transgenic mice reveal distal cis-regulatory elements governing BDNF gene expression.

Koppel Indrek I Aid-Pavlidis Tamara T Jaanson Kaur K Sepp Mari M Palm Kaia K Timmusk Tõnis T

Genesis (New York, N.Y. : 2000) 20100401 4

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 ge ...[more]

PMID: 20186743

Similar Datasets

Project description:The expression of prosaposin is temporally and spatially regulated at transcriptional and post-translational levels. Transgenic mice with various 5'-flanking deletions of the prosaposin promoter fused to luciferase (LUC) reporters were used to define its temporal regulatory region. LUC expression in the transgenic mice carrying constructs with 234 bp (234LUC), 310 bp (310LUC) or 2400 bp (2400LUC) of the 5'-flanking region was analysed in the central nervous system and eye throughout development. For 310LUC and 2400LUC, low-level LUC activity was maintained until embryonal day 18 in brain, eye and spinal cord. The peak level of LUC activity was at birth, with return to a plateau (1/3 of peak) throughout adulthood. Deletion of the region that included the retinoic acid-receptor-related orphan receptor (ROR alpha)-binding site and sequence-specific transcription factor (Sp1) cluster sites (44-310 bp) suppressed the peak of activity. By comparison, the peak level for 234LUC was shifted 2 weeks into neonatal life in the brain, but not in the eye, and no peak of activity was observed in the spinal cord. The endogenous prosaposin mRNA in eye, spinal cord and cerebellum had low-level expression before birth and continued to increase into adulthood. In cerebrum, the endogenous mRNA showed similar expression profile to constructs 310LUC, 2400LUC and 234LUC, with the peak expression at 1 week and a decreased level in adult. In the brain of the newborn, 2400LUC was highly expressed in the trigeminal ganglion and brain stem regions when compared with the generalized expression pattern for endogenous prosaposin mRNA. These results suggest that the modifiers (ROR alpha- and Sp1-binding sites) residing within 310 bp of the 5'-flanking region mediate developmental regulation in the central nervous system and eye. Additional regulatory elements outside the 5' region of the 2400 bp promoter fragment appear to be essential for the physiological control of the prosaposin locus.

Dataset Information

BAC transgenic mice reveal distal cis-regulatory elements governing BDNF gene expression.

Publications

BAC transgenic mice reveal distal cis-regulatory elements governing BDNF gene expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets