Slc4a10

PURPOSE: SLC4A10 encodes a plasma membrane-bound transporter, which mediates Na+ -dependent HCO3 - import thus mediating net acid extrusion. Slc4a10 knockout (KO) mice show collapsed brain ventricles, an increased seizure threshold, mild behavioral abnormalities, impaired vision, and deafness. METHODS: Utilizing exome/genome sequencing in families with undiagnosed neurodevelopmental disorders (NDD) and international data sharing, 11 patients from 6 independent families with biallelic variants in SLC4A10 were identified...

BACKGROUND: Carotid atherosclerosis is a chronic inflammatory disorder and is responsible for the vast majority of ischemic strokes. Inappropriate innate and adaptive immune responses synergize with malfunctional vascular wall cells to cause atherosclerotic lesions. Yet, functional characteristics of specific immune and endothelial cell subsets associated with atherosclerosis and cerebrovascular events are poorly understood. METHODS: Here, using single-cell RNA sequencing, the unprecedentedly largest data set from 20 patients' carotid artery plaques and paired peripheral blood mononuclear cells was generated, with which an ultra-high-precision cellular landscape of the atherosclerotic microenvironment involving 372 070 cells was depicted...

BACKGROUND AND PURPOSE: Diseases of raised intracranial pressure (ICP) cause severe morbidity and mortality. Multiple drugs are utilised to lower ICP including acetazolamide and topiramate. However, the evidence for their use is unclear. We aimed to assess the ICP modulatory effects and molecular effects at choroid plexus (CP) of acetazolamide and topiramate. EXPERIMENTAL APPROACH: Female rats were implanted with telemetric ICP probes for physiological, freely moving 24/7 ICP recordings...

SLC4A10 is a plasma-membrane bound transporter which utilizes the Na+ gradient to drive cellular HCO3- uptake, thus mediating acid extrusion. In the mammalian brain, SLC4A10 is expressed in principal neurons and interneurons, as well as in epithelial cells of the choroid plexus, the organ regulating the production of cerebrospinal fluid. Using next generation sequencing on samples from five unrelated families encompassing ten affected individuals, we show that biallelic SLC4A10 loss-of-function variants cause a clinically recognizable neurodevelopmental disorder in humans...

The kidney plays a central role in maintaining the fluid and electrolyte homeostasis in the body. Bicarbonate transporters NBCn1, NBCn2, and AE2 are expressed at the basolateral membrane of the medullary thick ascending limb (mTAL). In a previous study, NBCn1, NBCn2, and AE2 are proposed to play as a regulatory pathway to decrease NaCl reabsorption in the mTAL under high salt condition. When heterologously expressed, the activity of these transporters could be stimulated by the InsP3R binding protein released with inositol 1,4,5-trisphosphate (IRBIT), L-IRBIT (collectively the IRBITs), or protein phosphatase PP1...

Background: Idiopathic generalized epilepsy is the most common group of epilepsy disorders in children and adolescents. Various types of genetic abnormality were identified among the hereditary factors that explain epilepsy. Aims: To determine the variations in the etiopathogenesis, treatment protocol planning, and prognosis of idiopathic generalized epilepsy using the next-generation sequencing method. Study Design: A cross-sectional study...

Interstitial 2q24.2q24.3 microdeletions are rare cytogenetic aberrations associated with heterogeneous clinical features depending on the size of the deletion. Here, we describe 2 patients with overlapping de novo 2q24.2q24.3 deletions, characterized by array-CGH. This is the smallest 2q24.2q24.3 region of overlap described in the literature encompassing only 9 genes (SLC4A10, DPP4, GCG, FAP, IFIH1, GCA, KCNH7, FIGN, GRB14). We focused our attention on SLC4A10, DPP4, and KCNH7, genes associated with neurological features...

The choroid plexus (CP) is a small tissue located inside brain ventricles. It is responsible for the production of most of the cerebrospinal fluid (CSF); approximately 500 mL of CSF per day in the adult human [1, 2]. CSF production occurs as a net result of transcellular movement of salt and water, carried out by various cellular transporters. Ncbe is a sodium-coupled bicarbonate transporter located in the basolateral membrane of the choroid plexus epithelial (CPE) cells. It transports Na+ and HCO3 - into the cell in exchange for Cl- ...

The choroid plexus epithelium (CPE) has recently gained increasing interest as a potential target tissue to manipulating cerebrospinal fluid (CSF) production (1). It is therefore crucial to identify the basolateral Na+ transport mechanisms that are involved in CSF secretion, as it would be accessible from the blood side and thereby hold promise for pharmacological intervention. The sodium-bicarbonate transporter Ncbe has been identified as a basolateral Na+ importer in the CPE (2,3). Currently, there is no direct intracellular cation measurements in choroid plexus and this information is needed to establish Ncbe as the main basolateral Na+ importer...

The sea urchin embryo develops a calcitic endoskeleton through intracellular formation of amorphous calcium carbonate (ACC). Intracellular precipitation of ACC, requires [Formula: see text] concentrating as well as proton export mechanisms to promote calcification. These processes are of fundamental importance in biological mineralization, but remain largely unexplored. Here, we demonstrate that the calcifying primary mesenchyme cells (PMCs) use Na+ /H+ -exchange (NHE) mechanisms to control cellular pH homeostasis during maintenance of the skeleton...

Background: The idiopathic inflammatory myopathies (IIMs) are heterogeneous autoimmune conditions of skeletal muscle inflammation and weakness. MicroRNAs (miRNAs) are short, non-coding RNA which regulate gene expression of target mRNAs. The aim of this study was to profile miRNA and mRNA in IIM and identify miRNA-mRNA relationships which may be relevant to disease. Methods: mRNA and miRNA in whole blood samples from 7 polymyositis (PM), 7 dermatomyositis (DM), 5 inclusion body myositis and 5 non-myositis controls was profiled using next generation RNA sequencing...

BACKGROUND: Genetic disruption of slc4a10, which encodes the sodium-dependent chloride/bicarbonate exchanger Ncbe, leads to a major decrease in Na+ -dependent HCO3 - import into choroid plexus epithelial cells in mice and to a marked reduction in brain intraventricular fluid volume. This suggests that Ncbe functionally is a key element in vectorial Na+ transport and thereby for cerebrospinal fluid secretion in the choroid plexus. However, slc4a10 disruption results in severe changes in expression of Na+ ,K+ -ATPase complexes and other major transport proteins, indicating that profound cellular changes accompany the genetic manipulation...

Atherosclerosis and its comorbidities are the major contributors to the global burden of death worldwide. Lower extremities arterial disease (LEAD) is a common manifestation of atherosclerotic disease of arteries of lower extremities. MicroRNAs belong to epigenetic factors that regulate gene expression and have not yet been extensively studied in LEAD. We aimed to indicate the most promising microRNA and gene expression signatures of LEAD, to identify interactions between microRNA and genes and to describe potential effect of modulated gene expression...

The electroneutral Na+ /HCO3 - cotransporter NBCn2 (SLC4A10) of solute carrier family 4 (SLC4) plays important physiological and pathological roles in the body. Our previous study showed that NBCn2 is expressed on the protein level in the small intestine of rat. Here, by reverse-transcription polymerase chain reaction (PCR), we identified a novel full-length NBCn2 variant, i.e., NBCn2-K, from rat small intestine. By pHi measurement with Xenopus oocytes, the activity of NBCn2-K is not significantly different from NBCn2-G...

Background: To date, the pathogenesis of Meniere's disease (MD) remains unclear. Previous research found that the SLC4A1 gene significantly down-regulated. Aims : This study sought to understand the effect of SLC4A1 on the pathogenesis of MD. ELH C57 mice models were induced by intraperitoneal injection of AVP. Material and methods: The mRNA expression levels of SLC4A1, SLC4A10 and SLC26A4 were monitored by real-time quantitative PCR, the protein expression levels of SLC4A1 were monitored by immunoblotting and immunofluorescence before and after the ELH...

OBJECTIVE: The aim of this study was to use whole genome sequencing (WGS) help detect de novo mutations or pathogenic genes of Mayer-Rokitansky-Küster-Hauser syndrome type 1(MRKH syndrome type 1). STUDY DESIGN: This was a case-parent trios study. Nine unrelated probands, with MRKH syndrome type 1 and their parents were enrolled. The enrollment, sequencing process, establishment of the de novo mutations detecting procedure and experiment part were performed over a 2-year period...

The unique composition of the endolymph with a high extracellular K+ concentration is essential for sensory transduction in the inner ear. It is secreted by a specialized epithelium, the stria vascularis, that is connected to the fibrocyte meshwork of the spiral ligament in the lateral wall of the cochlea via gap junctions. In this study, we show that in mice the expression of the bicarbonate transporter Slc4a10/Ncbe/Nbcn2 in spiral ligament fibrocytes starts shortly before hearing onset. Its disruption in a C57BL/6 background results in early onset progressive hearing loss...

BACKGROUND: Mapping the breakpoints in de novo balanced chromosomal translocations (BCT) in symptomatic individuals provides a unique opportunity to identify in an unbiased way the likely causative genetic defect and thus find novel human disease candidate genes. Our aim was to fine-map breakpoints of de novo BCTs in a case series of nine patients. METHODS: Shallow whole-genome mate pair sequencing (SGMPS) together with long-range PCR and Sanger sequencing. In one case (BCT disrupting BAHD1 and RET ) cDNA analysis was used to verify expression of a fusion transcript in cultured fibroblasts...

Deletion of 2q24.2 is a rare cytogenetic aberration in patients, exhibiting heterogeneous clinical features, and common phenotypes included developmental delay, intellectual disability, hypotonia, and mild dysmorphic features. Hearing impairment and anal atresia are rarely described. Here we described a 9-month-old female patient with hypotonia in all four limbs, developmental delay, and intellectual disability. In addition, congenital anal atresia was diagnosed and treated after birth, and hearing impairment was found in right ear...

To date, the pathogenesis of Ménière's disease (MD) remains unclear. This study aims to investigate the possible relationship between potential immune system-related genes and sporadic MD. The whole RNA-sequencing (RNA-seq) technology was used to analyse the transcriptome of peripheral blood mononuclear cells of three MD patients and three control individuals. Of 366 differentially expressed genes (DEGs), 154 genes were up-regulated and 212 genes were down-regulated (|log2 fold change| > 1 and P < 0·05)...