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X-linked intellectual disability gene CASK regulates postnatal brain growth in a non-cell autonomous manner

Overview of attention for article published in Acta Neuropathologica Communications, March 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#36 of 363)
  • High Attention Score compared to outputs of the same age (87th percentile)
  • High Attention Score compared to outputs of the same age and source (84th percentile)

Mentioned by

news
1 news outlet
blogs
1 blog

Citations

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14 Dimensions

Readers on

mendeley
31 Mendeley
Title
X-linked intellectual disability gene CASK regulates postnatal brain growth in a non-cell autonomous manner
Published in
Acta Neuropathologica Communications, March 2016
DOI 10.1186/s40478-016-0295-6
Pubmed ID
Authors

Sarika Srivastava, Ryan McMillan, Jeffery Willis, Helen Clark, Vrushali Chavan, Chen Liang, Haiyan Zhang, Matthew Hulver, Konark Mukherjee

Abstract

The phenotypic spectrum among girls with heterozygous mutations in the X-linked intellectual disability (XLID) gene CASK (calcium/calmodulin-dependent serine protein kinase) includes postnatal microcephaly, ponto-cerebellar hypoplasia, seizures, optic nerve hypoplasia, growth retardation and hypotonia. Although CASK knockout mice were previously reported to exhibit perinatal lethality and a 3-fold increased apoptotic rate in the brain, CASK deletion was not found to affect neuronal physiology and their electrical properties. The pathogenesis of CASK associated disorders and the potential function of CASK therefore remains unknown. Here, using Cre-LoxP mediated gene excision experiments; we demonstrate that deleting CASK specifically from mouse cerebellar neurons does not alter the cerebellar architecture or function. We demonstrate that the neuron-specific deletion of CASK in mice does not cause perinatal lethality but induces severe recurrent epileptic seizures and growth retardation before the onset of adulthood. Furthermore, we demonstrate that although neuron-specific haploinsufficiency of CASK is inconsequential, the CASK mutation associated human phenotypes are replicated with high fidelity in CASK heterozygous knockout female mice (CASK ((+/-))). These data suggest that CASK-related phenotypes are not purely neuronal in origin. Surprisingly, the observed microcephaly in CASK ((+/-)) animals is not associated with a specific loss of CASK null brain cells indicating that CASK regulates postnatal brain growth in a non-cell autonomous manner. Using biochemical assay, we also demonstrate that CASK can interact with metabolic proteins. CASK knockdown in human cell lines cause reduced cellular respiration and CASK ((+/-)) mice display abnormalities in muscle and brain oxidative metabolism, suggesting a novel function of CASK in metabolism. Our data implies that some phenotypic components of CASK heterozygous deletion mutation associated disorders represent systemic manifestation of metabolic stress and therefore amenable to therapeutic intervention.

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 8 26%
Student > Ph. D. Student 6 19%
Researcher 5 16%
Student > Master 5 16%
Student > Doctoral Student 3 10%
Other 4 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 29%
Neuroscience 7 23%
Psychology 4 13%
Medicine and Dentistry 4 13%
Agricultural and Biological Sciences 3 10%
Other 3 10%
Unknown 1 3%

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 25 May 2016.
All research outputs
#623,741
of 7,757,128 outputs
Outputs from Acta Neuropathologica Communications
#36
of 363 outputs
Outputs of similar age
#32,488
of 268,890 outputs
Outputs of similar age from Acta Neuropathologica Communications
#4
of 32 outputs
Altmetric has tracked 7,757,128 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 363 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has done well, scoring higher than 89% of its peers.
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 268,890 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 32 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.