Biology subjects

Kang, S. K.

Publications and source records attributed to Kang, S. K..

3 recordsLinked to original sources

bioRxiv2023

Altered neurological and neurobehavioral phenotypes in a mouse model of the recurrent KCNB1-p.R306C voltage-sensor variant

Pathogenic variants in KCNB1 are associated with a neurodevelopmental disorder spectrum that includes global developmental delays, cognitive impairment, abnormal electroencephalogram (EEG) patterns, and epilepsy with variable age of onset and severity. Additionally, there are prominent behavioral disturbances, including hyperactivity, aggression, and features of autism spectrum disorder. The most frequently identified recurrent variant is KCNB1-p.R306C, a missense variant located within the S4 voltage-sensing transmembrane domain. Individuals with the R306C variant exhibit mild to severe developmental delays, behavioral disorders, and a diverse spectrum of seizures. Previous in vitro characterization of R306C described loss of voltage sensitivity and cooperativity of the sensor and inhibition of repetitive firing. Existing Kcnb1 mouse models include dominant negative missense variants, as well as knockout and frameshifts alleles. While all models recapitulate key features of KCNB1 encephalopathy, mice with dominant negative alleles were more severely affected. In contrast to existing loss-of-function and dominant-negative variants, KCNB1-p.R306C does not affect channel expression, but rather affects voltage-sensing. Thus, modeling R306C in mice provides a novel opportunity to explore impacts of a voltage-sensing mutation in Kcnb1. Using CRISPR/Cas9 genome editing, we generated the Kcnb1R306C mouse model and characterized the molecular and phenotypic effects. Heterozygous and homozygous R306C mice exhibited pronounced hyperactivity, altered susceptibility to flurothyl and kainic acid induced-seizures, and frequent, long runs of spike wave discharges on EEG. This novel model of channel dysfunction in Kcnb1 provides an additional, valuable tool to study KCNB1 encephalopathies. Furthermore, this allelic series of Kcnb1 mouse models will provide a unique platform to evaluate targeted therapies.

neuroscience↗

bioRxiv2020

Newly developed silicone airway stent (GINA stent): Mechanical characteristics and performance evaluation in pigs

OBJECTIVESCentral airway obstruction (CAO) is caused by various malignant and benign processes. Surgery is a preferred option for CAO, but if not possible, bronchoscopic treatment could be performed. Recently, bronchoscopic treatments have been improved. Particularly in airway stents, new attempts are being made to overcome the existing shortcomings of stents (migration, mucostasis, and granulation tissue formation). We recently developed a new silicone airway stent (GINA stent). The GINA stent has anti-migration design, dynamic structure enabling reduction of stent cross-sectional area, and radiopaqueness. We sought to evaluate mechanical characteristics and performance of our novel GINA stent in a pig tracheal stenosis model. METHODSAll tests were performed by comparing GINA stent [outer diameter (OD, mm) 14, length (L, mm) 55] with Dumon stent (OD14L50). Mechanical tests were done using digital force gage to determine the anti-migration force, expansion force, and flexibility. Short-term (3 weeks) performance was evaluated after stent implantations [GINA (n = 4) vs. Dumon (n = 3)] in a pig model of tracheal stenosis. RESULTSMechanical properties outcomes for GINA vs. Dumon: anti-migration force [18.4 vs. 12.8 Newton (N)]; expansion force (11.9 vs. 14.5 N); flexibility (3.1 vs. 4.5 N). Short-term (3 weeks) GINA vs. Dumon performances: mucus retention (0/4 vs. 0/3); granulation tissue formation (0/4 vs. 0/3); migration (1/4 vs. 2/3). CONCLUSIONSGINA stent demonstrated better mechanical properties than Dumon stent with a stent performance not inferior to Dumon stent.

physiology↗

bioRxiv2019

High throughput Characterization of KCNB1 variants Associated with Developmental and Epileptic Encephalopathy

Pathogenic variants in KCNB1, encoding the voltage-gated potassium channel Kv2.1, are associated with developmental and epileptic encephalopathies (DEE). Previous functional studies on a limited number of KCNB1 variants indicated a range of molecular mechanisms by which variants affect channel function, including loss of voltage sensitivity, loss of ion selectivity, and reduced cell-surface expression. We evaluated a series of 17 KCNB1 variants associated with DEE or neurodevelopmental disorder (NDD) to rapidly ascertain channel dysfunction using high-throughput functional assays. Specifically, we investigated the biophysical properties and cell-surface expression of variant Kv2.1 channels expressed in heterologous cells using high-throughput automated electrophysiology and immunocytochemistry-flow cytometry. Pathogenic variants exhibited diverse functional defects, including altered current density and shifts in the voltage-dependence of activation and/or inactivation, as homotetramers or when co-expressed with wild-type Kv2.1. Quantification of protein expression also identified variants with reduced total Kv2.1 expression or deficient cell-surface expression.\n\nOur study establishes a platform for rapid screening of functional defects of KCNB1 variants associated with DEE and other NDDs, which will aid in establishing KCNB1 variant pathogenicity and may enable discovery of targeted strategies for therapeutic intervention based on molecular phenotype.

genetics↗