Transgenic targeting with regulatory elements of the humanCD34 gene

Radomska, Hanna S.; González, David; Okuno, Yutaka; Iwasaki, Hiromi; Nagy, András; Akashi, Koichi; Tenen, Daniel G.; Huettner, Claudia S.

doi:10.1182/blood-2002-02-0355

Cited by 44 publications

(55 citation statements)

References 62 publications

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“…The first transgene consists of the NSE promoter driving the expression of the tTA, which is inhibited by tetracycline (14). These mice were crossed with mice that contain a transgene consisting of the TetOp promoter (which is activated by tTA) driving expression of Cre recombinase (15,16). These bigenic NSE-tTA ϫ TetOp-Cre mice were then crossed with mice containing a floxed BDNF locus (13) to generate the inducible KO mice ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The neuronspecific enolase-tetracycline transcriptional activator (NSEtTA) line are on a BL6͞SJL ϫ ICR background, the TetOp-Cre are on an ICR background, and the floxed BDNF mice are on a BL6͞sv129 background. The NSE-tTA mice (14) and the TetOp-Cre mice (15,16) were maintained as homozygotes then crossed to generate the bigenic mice. The floxed LacZ reporter mice (17) or floxed BDNF mice (13) were then crossed with the bigenic NSE-tTA͞TetOp-Cre mice to generate the inducible KO mice.…”

Section: Methodsmentioning

confidence: 99%

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Essential role of brain-derived neurotrophic factor in adult hippocampal function

Monteggia

Barrot

Powell

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

616

442

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Brain-derived neurotrophic factor (BDNF) regulates neuronal development and function. However, it has been difficult to discern its role in the adult brain in influencing complex behavior. Here, we use a recently developed inducible knockout system to show that deleting BDNF in broad forebrain regions of adult mice impairs hippocampal-dependent learning and long-term potentiation. We use the inducible nature of this system to show that the loss of BDNF during earlier stages of development causes hyperactivity and more pronounced hippocampal-dependent learning deficits. We also demonstrate that the loss of forebrain BDNF attenuates the actions of desipramine, an antidepressant, in the forced swim test, suggesting the involvement of BDNF in antidepressant efficacy. These results establish roles for BDNF in the adult, and demonstrate the strength of this inducible knockout system in studying gene function in the adult brain.B rain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors (1, 2). It is widely expressed in the mammalian brain (3) and regulates many aspects of neuronal function (4-8). However, a role for BDNF in regulating complex behavior has been difficult to assess, because of the lack of specific pharmacological agents and the early postnatal lethality of BDNF null (Ϫ͞Ϫ) mice (9). Studies examining heterozygous BDNF (ϩ͞Ϫ) mice, which display roughly half the normal levels of BDNF in brain, have reported increased feeding behavior, obesity, hyperactivity, and aggressiveness (10-12). However, these alterations may arise from developmental abnormalities and complicate the interpretation of the role of BDNF in the adult brain.The recent generation of conditional BDNF knockout (KO) mice circumvents the problem of postnatal lethality and allows for some regional specificity of gene deletion. For example, conditional BDNF KO mice survive to adulthood and exhibit a range of deficits similar to those seen in the heterozygous null mice (13). However, such conditional KO mice still suffer from the fact that they delete a gene of interest during late-embryonic or early postnatal periods and thus do not preclude developmental abnormalities as the cause of behavioral impairments observed. This is of a particular concern in studying complex behavior because early developmental periods in humans are crucial for the manifestation of many complex neuropsychiatric illnesses. To truly investigate the influence of BDNF on complex behavior in adults, it is necessary to have a system in which BDNF is deleted in an inducible manner in specific brain regions. We have generated an inducible KO system in which BDNF can be deleted selectively in the brain of adult mice. Here we describe the phenotype of mice in which BDNF has been deleted in broad forebrain regions of adult mice. We use the inducibility of the system to examine the phenotype of mice in which BDNF has been deleted at earlier stages of development in the same brain regions. Our results demonstrate that the role of BDNF in the ...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Essential role of brain-derived neurotrophic factor in adult hippocampal function

Monteggia

Barrot

Powell

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

616

442

View full text Add to dashboard Cite

show abstract

“…11,12 To generate the animals for the current experimental series, two geneticallyaltered, independently-derived mouse strains were used. Reduction of BDNF expression was achieved using an inducible knockout (KO) of the BDNF gene where two transgenes, the tetracycline transactivator (tTA) gene driven by neuron-specific enolase (NSE) promoter (nse-tTA) 16 and the Cre recombinase gene under the control of tTA-responsive tetO promoter (tetO-cre) 17,18 regulate the deletion of floxed exon V of BNDF 19 in a tetracycline-dependent manner. The two mouse lines with NSE-tTA and tetO-cre transgenes were both maintained as homozygotes.…”

Section: Methodsmentioning

confidence: 99%

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

et al. 2006

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“…As shown by Schönig et al (Schönig et al, 2002), this mouse line was used in the triple transgenic mouse system based on tet-Cre crossed to a reporter line as we propose here. Alternatively, Tet-O-Cre transgenic mice, which expresses Cre-recombinase in a TRE-dependent manner, might be used (Hsu et al, 2010;Le et al, 2008;Radomska et al, 2002;Tang et al, 2008). The offspring of this mating are called "tet-Cre mice".…”

Section: A Potential Lineage Tracing Study To Monitor Contribution Ofmentioning

confidence: 99%

Are We There Yet? A Story About Cardiac Stem Cells

Uchida¹,

Gaspari²,

Braun³

2011

Stem Cells in Clinic and Research

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Transgenic targeting with regulatory elements of the humanCD34 gene

Cited by 44 publications

References 62 publications

Essential role of brain-derived neurotrophic factor in adult hippocampal function

Essential role of brain-derived neurotrophic factor in adult hippocampal function

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

Are We There Yet? A Story About Cardiac Stem Cells

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