Article

Expression of myoglobin in the transgenic mouse brain.

Department of Biomedical Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA.
Advances in experimental medicine and biology (impact factor: 1.09). 02/2003; 530:331-45.
Source: PubMed

ABSTRACT The main purpose of this study was to express human myoglobin in mouse brain neurons and investigate the effects of this expression on metabolism and blood flow using phosphorous (31P) NMR spectroscopy and NMR perfusion imaging. Transgenic mice expressing brain myoglobin were created using a cDNA sequence for human myoglobin placed under the transcriptional control of either a human platelet-drived grown factor polypeptide B (PDGF-B) promoter sequence or a rat neuron-specific enolase (NSE) promoter sequence. The presence of myoglobin having a functional, reduced-state, heme group was demonstrated by protein analysis and immunocytochemistry. Expression levels were highest in the hippocampus, cerebellum, and cerebral cortex. No gross morphological adaptations of neural tissue resulting from the expression were observed and no statistically significant differences in the energetic state, as measured by 31P NMR, or baseline cortical perfusion, as measured by an NMR perfusion imaging technique, were found.

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    Article: Genetically controlled MRI contrast mechanisms and their prospects in systems neuroscience research.
    Gil G Westmeyer, Alan Jasanoff
    [show abstract] [hide abstract]
    ABSTRACT: Application of MRI contrast agents to neural systems research is complicated by the need to deliver agents past the blood-brain barrier or into cells, and the difficulty of targeting agents to specific brain structures or cell types. In the future, these barriers may be wholly or partially overcome using genetic methods for producing and directing MRI contrast. Here we review MRI contrast mechanisms that have used gene expression to manipulate MRI signal in cultured cells or in living animals. We discuss both fully genetic systems involving endogenous biosynthesis of contrast agents, and semi-genetic systems in which expressed proteins influence the localization or activity of exogenous contrast agents. We close by considering which contrast-generating mechanisms might be most suitable for applications in neuroscience, and we ask how genetic control machinery could be productively combined with existing molecular agents to enable next-generation neuroimaging experiments.
    Magnetic Resonance Imaging 08/2007; 25(6):1004-10. · 1.99 Impact Factor
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Keywords

baseline cortical perfusion
 
blood flow
 
brain myoglobin
 
cerebellum
 
cerebral cortex
 
energetic state
 
factor polypeptide B
 
human myoglobin
 
metabolism
 
mouse brain neurons
 
myoglobin
 
neural tissue
 
NMR perfusion imaging
 
NMR perfusion imaging technique
 
PDGF-B
 
protein analysis
 
rat neuron-specific enolase
 
statistically significant differences
 
transcriptional control
 
Transgenic mice
 

Ross D Shonat