Double Xp11.22 deletion including SHROOM4 and CLCN5 associated with severe psychomotor retardation and Dent disease

Armanet, Narjes; Métay, Corinne; Brisset, Sophie; Deschenes, Georges; Pineau, Dominique; Petit, François; Rocco, Federico Di; Goossens, Michel; Tachdjian, Gérard; Labrune, Philippe; Tosca, Lucie

doi:10.1186/s13039-015-0107-x

Cited by 16 publications

(21 citation statements)

References 20 publications

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“…In addition, a pathogenic missense mutation was identified in an unrelated large family, with carriers exhibiting mild-to-severe intellectual disability (ID) and increased susceptibility to seizures25. Recent studies reinforce the role of Shrm4 in ID678, however, how disruption of KIAA1202 causes these neuropathological conditions is unknown. Indeed, the role of Shrm4 in the brain is also unknown, but given the pathological profile, it may regulate GABA-mediated inhibition910.…”

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confidence: 99%

Epilepsy and intellectual disability linked protein Shrm4 interaction with GABABRs shapes inhibitory neurotransmission

et al. 2017

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Shrm4, a protein expressed only in polarized tissues, is encoded by the KIAA1202 gene, whose mutations have been linked to epilepsy and intellectual disability. However, a physiological role for Shrm4 in the brain is yet to be established. Here, we report that Shrm4 is localized to synapses where it regulates dendritic spine morphology and interacts with the C terminus of GABAB receptors (GABABRs) to control their cell surface expression and intracellular trafficking via a dynein-dependent mechanism. Knockdown of Shrm4 in rat severely impairs GABABR activity causing increased anxiety-like behaviour and susceptibility to seizures. Moreover, Shrm4 influences hippocampal excitability by modulating tonic inhibition in dentate gyrus granule cells, in a process involving crosstalk between GABABRs and extrasynaptic δ-subunit-containing GABAARs. Our data highlights a role for Shrm4 in synaptogenesis and in maintaining GABABR-mediated inhibition, perturbation of which may be responsible for the involvement of Shrm4 in cognitive disorders and epilepsy.

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confidence: 99%

Epilepsy and intellectual disability linked protein Shrm4 interaction with GABABRs shapes inhibitory neurotransmission

et al. 2017

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“…SHROOM4, which takes part in the process of cytoskeletal organization, was reported critical for human brain structures and survival of some specific neuronal cell types [113]. The deletion of the SHROOM4 gene was believed may contribute to severe psychomotor retardation and Dent disease [114]. We observed the SHROOM4 gene was highly and specifically expressed in the pig cells of C0 (OLG) and C3 (OLG), while deprived in the mouse cells (Figure 4f).…”

Section: Divergence Of Brain Functions In Pig and Mousementioning

confidence: 66%

Single cell atlas of domestic pig brain illuminates the conservation and divergence of cell types at spatial and species levels

Chen

Zhu

Zhong

et al. 2019

Preprint

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Domestic pig (Sus scrofa domesticus) has drawn much attention from researchers worldwide due to its implications in evolutionary biology, regenerative medicine and agriculture. The brain atlas of Homo sapiens (primate), Mus musculus (rodent), Danio rerio (fish) and Drosophila melanogaster (insect) have been constructed at single cell resolution, however, the cellular compositions of pig brain remain largely unexplored. In this study, we investigated the single-cell transcriptomic profiles of five distinct regions of domestic pig brain, from which we identified 21 clusters corresponding to six major cell types, characterized by unique spectrum of gene expression. By spatial comparison, we identified cell types enriched or depleted in certain brain regions. Inter-species comparison revealed cell-type similarities and divergences in hypothalamus between mouse and pig, providing invaluable resources for the evolutionary exploration of brain functions at single cell level. Besides, our study revealed cell types and molecular pathways closely associated with several diseases (obesity, anorexia, bulimia, epilepsy, intellectual disability, and autism spectrum disorder), bridging the gap between gene mutations and pathological phenotypes, which might be of great use to the development precise therapies against neural system disorders. Taken together, we reported, so far as we know, the first single cell brain atlas of Sus scrofa domesticus, followed by comprehensive comparisons across brain region and species, which could throw light upon future evo-devo, regenerative medicine, and agricultural studies. Introduction:The domestic pig (Sus scrofa domesticus), one of the most important livestocks, shares close interaction relationships with humans during evolution history [1][2][3]. It belongs to the eutherian mammal from cetartiodactyla order, a clade distinct from primates and rodents [4]. Domestic pig has been widely studied because of its significances in evolutionary biology and regenerative medicine [5]. During the past decades, pig is increasingly used in neuroscience researches, due to the much higher correspondence in its brain to human brain in anatomy, physiology, and development than that of commonly used small laboratory animals such as mouse and rat [6,7]. Similar to human brain, pig brain is gyrencephalic and easy to recognize anatomically. For example, the cerebral cortex is clearly differentiated into four lobes including temporal lobe (TL), frontal lobe (FL), parital lobe (PL), and occipital lobe (OL) [8]. Recently, a transgenetic pig Huntington's disease (HD) model was established by a mutant huntingtin knockin, who shows classical HD phenotypes such as behavioral abnormalities, consistent movement and early death [9]. Accumulating genetic manipulation tools have facilitated the applications of pig as an animal model for researches into brain function, particularly studies concerning brain malfunctioning mechanism. Besides, for ethical and economical reasons, pig is a more acceptable lab animal than primat...

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“…Shroom‐protein binding regulates the distribution and activity of rho kinase (rock), which influences cellular morphology and tissue morphogenesis via the actomyosin network . Shroom appears to play a role in cancer, neural‐tube defects, chronic kidney disease, and X‐linked intellectual disability . The shroom–rock interaction is thus interesting from a biological and medical perspective.…”

Section: Resultsmentioning

confidence: 99%

Pyrite: A blender plugin for visualizing molecular dynamics simulations using industry‐standard rendering techniques

Rajendiran

Durrant

2017

J Comput Chem

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Molecular dynamics (MD) simulations provide critical insights into many biological mechanisms. Programs such as VMD, Chimera, and PyMOL can produce impressive simulation visualizations, but they lack many advanced rendering algorithms common in the film and video-game industries. In contrast, the modeling program Blender includes such algorithms but cannot import MD-simulation data. MD trajectories often require many gigabytes of memory/disk space, complicating Blender import. We present Pyrite, a Blender plugin that overcomes these limitations. Pyrite allows researchers to visualize MD simulations within Blender, with full access to Blender's cutting-edge rendering techniques. We expect Pyrite-generated images to appeal to students and non-specialists alike. A copy of the plugin is available at http://durrantlab.com/pyrite/, released under the terms of the GNU General Public License Version 3. © 2017 Wiley Periodicals, Inc.

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Double Xp11.22 deletion including SHROOM4 and CLCN5 associated with severe psychomotor retardation and Dent disease

Cited by 16 publications

References 20 publications

Epilepsy and intellectual disability linked protein Shrm4 interaction with GABABRs shapes inhibitory neurotransmission

Epilepsy and intellectual disability linked protein Shrm4 interaction with GABABRs shapes inhibitory neurotransmission

Single cell atlas of domestic pig brain illuminates the conservation and divergence of cell types at spatial and species levels

Pyrite: A blender plugin for visualizing molecular dynamics simulations using industry‐standard rendering techniques

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