Disruption of Src Is Associated with Phenotypes Related to Williams-Beuren Syndrome and Altered Cellular Localization of TFII-I

Sinai, Laleh; Ivakine, Evgueni A.; Lam, Emily; Deurloo, Marielle; Dida, Joana; Zirngibl, Ralph A; Jung, Cynthia C.; Aubin, Jane E.; Feng, Zhong‐Ping; Yeomans, John S.; McInnes, Roderick R.; Osborne, Lucy R.; Roder, John

doi:10.1523/eneuro.0016-14.2015

Cited by 11 publications

(9 citation statements)

References 67 publications

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“…CD animals fed with EGCG presented normalized expression levels of Bdnf without any effect in neuroanatomical remodeling. It has been shown that the membrane localization of TRPC3 channels, important mediators of BDNF-mediated Ca 2+ signal generation and dendritic remodeling [ 46 ], is regulated by general transcription factor TFII-I encoded by GTF2I deleted in WBS[ 33 , 34 ]. In hippocampal primary cultures of CD mice we observed altered intracellular calcium flux although no significant changes in TRPC3 distribution were observed.…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-gallate improves cardiac hypertrophy and short-term memory deficits in a Williams-Beuren syndrome mouse model

et al. 2018

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Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a heterozygous deletion of 26–28 genes at chromosome band 7q11.23. The complete deletion (CD) mouse model mimics the most common deletion found in WBS patients and recapitulates most neurologic features of the disorder along with some cardiovascular manifestations leading to significant cardiac hypertrophy with increased cardiomyocytes’ size. Epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, has been associated with potential health benefits, both on cognition and cardiovascular phenotypes, through several mechanisms. We aimed to investigate the effects of green tea extracts on WBS-related phenotypes through a phase I clinical trial in mice. After feeding CD animals with green tea extracts dissolved in the drinking water, starting at three different time periods (prenatal, youth and adulthood), a set of behavioral tests and several anatomical, histological and molecular analyses were performed. Treatment resulted to be effective in the reduction of cardiac hypertrophy and was also able to ameliorate short-term memory deficits of CD mice. Taken together, these results suggest that EGCG might have a therapeutic and/or preventive role in the management of WBS.

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Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-gallate improves cardiac hypertrophy and short-term memory deficits in a Williams-Beuren syndrome mouse model

et al. 2018

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“…4D ) ( 66 ). In order to assess whether the phosphorylation seen in TFII-I is observed in GTF2IRD1, reported phosphorylation sites in TFII-I were searched for in GTF2IRD1 ( 67 – 69 ). TFII-I contained two consensus Src-dependent tyrosine phosphorylation sites with two additional Src homology-binding motifs ( 67 ).…”

Section: Discussionmentioning

confidence: 99%

Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon

Kayama

Mori

Ito

et al. 2016

Molecular and Cellular Biology

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Mechanoforces experienced by an organ are translated into biological information for cellular sensing and response. In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turnover. We show that Mohawk (Mkx), a tendon-specific transcription factor, is essential in mechanoresponsive tenogenesis through regulation of its downstream ECM genes such as type I collagens and proteoglycans such as fibromodulin both in vivo and in vitro. Wild-type (WT) mice demonstrated an increase in collagen fiber diameter and density in response to physical treadmill exercise, whereas in Mkx−/− mice, tendons failed to respond to the same mechanical stimulation. Furthermore, functional screening of the Mkx promoter region identified several upstream transcription factors that regulate Mkx. In particular, general transcription factor II-I repeat domain-containing protein 1 (Gtf2ird1) that is expressed in the cytoplasm of unstressed tenocytes translocated into the nucleus upon mechanical stretching to activate the Mkx promoter through chromatin regulation. Here, we demonstrate that Gtf2ird1 is essential for Mkx transcription, while also linking mechanical forces to Mkx-mediated tendon homeostasis and regeneration.

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“…Muscle tension was measured by grip strength test described previously with minor modifications ( 42 ). Briefly, grip strength was measured by recording latency of time the mouse was able to hold on a steel wire (9.0 mm in diameter, 50.0 mm in length) suspended 40.0 cm above the horizontal surface of the ground.…”

Section: Methodsmentioning

confidence: 99%

ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death

Liu

Hong

et al. 2018

Front. Immunol.

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Amyotrophic Lateral Sclerosis (ALS) is a group of neurodegenerative disorders that featured with the death of motor neurons, which leads to loss of voluntary control on muscles. The etiologies vary among different subtypes of ALS, and no effective management or medication could be provided to the patients, with the underlying mechanisms incompletely understood yet. Mutations in human Optn (Optineurin), particularly E478G, have been found in many ALS patients. In this work, we report that NF-κB activity was increased in Optn knockout (Optn−/−) MEF (mouse embryonic fibroblast) cells expressing OPTN of different ALS-associated mutants especially E478G. Inflammation was significantly activated in mice infected with lenti-virus that allowed overexpression of OPTNE478G mutation in the motor cortex, with marked increase in the secretion of pro-inflammatory cytokines as well as neuronal cell death. Our work with both cell and animal models strongly suggested that anti-inflammation treatment could represent a powerful strategy to intervene into disease progression in ALS patients who possess the distinctive mutations in OPTN gene.

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Disruption of Src Is Associated with Phenotypes Related to Williams-Beuren Syndrome and Altered Cellular Localization of TFII-I

Cited by 11 publications

References 67 publications

Epigallocatechin-3-gallate improves cardiac hypertrophy and short-term memory deficits in a Williams-Beuren syndrome mouse model

Epigallocatechin-3-gallate improves cardiac hypertrophy and short-term memory deficits in a Williams-Beuren syndrome mouse model

Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon

ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death

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