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A novel vector for transgenesis in the rat CNS

Overview of attention for article published in Acta Neuropathologica Communications, November 2017
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Title
A novel vector for transgenesis in the rat CNS
Published in
Acta Neuropathologica Communications, November 2017
DOI 10.1186/s40478-017-0484-y
Pubmed ID
Authors

T. Peter Lopez, Kurt Giles, Brittany N. Dugger, Abby Oehler, Carlo Condello, Zuzana Krejciova, Julian A. Castaneda, George A. Carlson, Stanley B. Prusiner

Abstract

The larger brain of the rat enables a much greater repertoire of complex behaviors than mice, likely making rats preferential for investigating neurodegeneration. Because molecular tools for specific expression of transgenes in the rat brain are sparse, we chose Prnp encoding the prion protein (PrP) to develop a novel vector to drive transgene expression in the rat brain. We compared the rat Prnp sequence with mouse and Syrian hamster Prnp sequences, identifying conserved genetic elements and hypothesizing that these elements would be able to drive neuronal transgene expression. We investigated this by generating a vector termed RaPrnp that encompasses portions of the rat Prnp gene. Importantly, we replaced the rat Prnp open reading frame (ORF) with a cloning site for rapid and seamless In-Fusion cloning. To validate the in vivo neuronal specificity of the RaPrnp vector in rats, we generated stable RaPrnp-LacZ/enhanced green fluorescent protein (EGFP) transgenic (Tg) rat lines, which led to robust LacZ activity and high EGFP fluorescence in the central nervous system of embryos and adult animals. Next, we restored the rat Prnp ORF and generated multiple Tg(RaPrnp-PrP) lines, demonstrating that overexpression of Prnp accelerates the onset of scrapie. While the incubation time in wild-type (WT) rats was 175 ± 3 days post inoculation (dpi), one line, Tg2919, overexpressed RaPrP(C) at 4.4-fold and exhibited a reduced incubation time of 149 ± 2 dpi. The second line, Tg2922, overexpressed RaPrP(C) at 9.7-fold compared with WT animals and had an incubation time of 112 ± 0 dpi. Tg2922 rats inoculated with rat RML showed extensive vacuolation of the brainstem in contrast to WT and Tg2919 animals in which vacuolation was most prominent in the hippocampus and striatum as well as the motor and sensory cortices. It is possible that construction of Tg rats with modified phenotypes will prove more advantageous than mice for neurodegeneration studies.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 25 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 28%
Researcher 4 16%
Student > Bachelor 3 12%
Student > Master 2 8%
Lecturer > Senior Lecturer 1 4%
Other 2 8%
Unknown 6 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 12%
Medicine and Dentistry 2 8%
Social Sciences 2 8%
Agricultural and Biological Sciences 1 4%
Computer Science 1 4%
Other 6 24%
Unknown 10 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 July 2018.
All research outputs
#14,831,338
of 23,008,860 outputs
Outputs from Acta Neuropathologica Communications
#1,121
of 1,394 outputs
Outputs of similar age
#247,958
of 437,733 outputs
Outputs of similar age from Acta Neuropathologica Communications
#21
of 30 outputs
Altmetric has tracked 23,008,860 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,394 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one is in the 19th percentile – i.e., 19% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 437,733 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 30 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.