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Haploinsufficient TNAP Mice Display Decreased Extracellular ATP Levels and Expression of Pannexin-1 Channels

Overview of attention for article published in Frontiers in Pharmacology, March 2018
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Title
Haploinsufficient TNAP Mice Display Decreased Extracellular ATP Levels and Expression of Pannexin-1 Channels
Published in
Frontiers in Pharmacology, March 2018
DOI 10.3389/fphar.2018.00170
Pubmed ID
Authors

Álvaro Sebastián-Serrano, Laura de Diego-García, David C. Henshall, Tobías Engel, Miguel Díaz-Hernández

Abstract

Hypophosphatasia (HPP) is a rare heritable metabolic bone disease caused by hypomorphic mutations in theALPL(in human) orAkp2(in mouse) gene, encoding the tissue-nonspecific alkaline phosphatase (TNAP) enzyme. In addition to skeletal and dental malformations, severe forms of HPP are also characterized by the presence of spontaneous seizures. Initially, these seizures were attributed to an impairment of GABAergic neurotransmission caused by altered vitamin B6 metabolism. However, recent work by our group using knockout mice null for TNAP (TNAP-/-), a well-described model of infantile HPP, has revealed a deregulation of purinergic signaling contributing to the seizure phenotype. In the present study, we report that adult heterozygous (TNAP+/-) transgenic mice with decreased TNAP activity in the brain are more susceptible to adenosine 5'-triphosphate (ATP)-induced seizures. Interestingly, when we analyzed the extracellular levels of ATP in the cerebrospinal fluid, we found that TNAP+/- mice present lower levels than control mice. To elucidate the underlying mechanism, we evaluated the expression levels of other ectonucleotidases, as well as different proteins involved in ATP release, such as pannexin, connexins, and vesicular nucleotide transporter. Among these, Pannexin-1 (Panx1) was the only one showing diminished levels in the brains of TNAP+/- mice. Altogether, these findings suggest that a physiological regulation of extracellular ATP levels and Panx1 changes may compensate for the reduced TNAP activity in this model of HPP.

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Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 26%
Other 3 16%
Lecturer 1 5%
Lecturer > Senior Lecturer 1 5%
Professor 1 5%
Other 3 16%
Unknown 5 26%
Readers by discipline Count As %
Neuroscience 4 21%
Medicine and Dentistry 2 11%
Biochemistry, Genetics and Molecular Biology 1 5%
Nursing and Health Professions 1 5%
Computer Science 1 5%
Other 3 16%
Unknown 7 37%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 20 March 2018.
All research outputs
#17,932,482
of 23,025,074 outputs
Outputs from Frontiers in Pharmacology
#7,211
of 16,334 outputs
Outputs of similar age
#241,104
of 331,404 outputs
Outputs of similar age from Frontiers in Pharmacology
#168
of 359 outputs
Altmetric has tracked 23,025,074 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,334 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
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We're also able to compare this research output to 359 others from the same source and published within six weeks on either side of this one. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.