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BAC transgenic mice reveal distal cis‐regulatory elements governing BDNF gene expression
Author(s) -
Koppel Indrek,
AidPavlidis Tamara,
Jaanson Kaur,
Sepp Mari,
Palm Kaia,
Timmusk Tõnis
Publication year - 2010
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20606
Subject(s) - biology , exon , transgene , neurotrophic factors , brain derived neurotrophic factor , genetically modified mouse , promoter , microbiology and biotechnology , gene , bacterial artificial chromosome , glial cell line derived neurotrophic factor , tropomyosin receptor kinase b , gene expression , genetics , receptor , genome
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. genesis 48:214–219, 2010. © 2010 Wiley‐Liss, Inc.