Ask about this productRelated genes to: KCNV2 antibody
- Gene:
- KCNV2 NIH gene
- Name:
- potassium voltage-gated channel modifier subfamily V member 2
- Previous symbol:
- -
- Synonyms:
- Kv8.2
- Chromosome:
- 9p24.2
- Locus Type:
- gene with protein product
- Date approved:
- 2002-11-20
- Date modifiied:
- 2016-02-04
Related products to: KCNV2 antibody
Related articles to: KCNV2 antibody
- Photoreceptors are highly energy-demanding neurons, and disruption of photoreceptor signaling remodels retinal metabolism and contributes to degeneration, yet the pathways underlying these changes remain incompletely defined. Kv8.2 knockout (KO) mice, a model of KCNV2 retinopathy, exhibit impaired photoreceptor ion homeostasis and slow rod degeneration, providing an opportunity to investigate metabolic adaptation during progressive dysfunction. Untargeted metabolomic profiling was performed on retinas from wildtype (WT) and Kv8.2 KO mice at 1 and 13 months of age. Principal component analysis revealed distinct profiles for aged Kv8.2 KO retinas compared with aged WT and young groups, while young WT and KO retinas were metabolically similar. The major changes in aged Kv8.2 KO retinas compared to aged WT were reduced nucleobases and nucleosides while the amino acids homocysteine, methionine, and serine were elevated. These are signature metabolites in one-carbon metabolism, a metabolic hub influencing nucleotide metabolism, epigenic regulation, and anti-oxidant defense. Supervised modeling showed that these one-carbon-related changes emerge early and progress with age in Kv8.2 KO retinas. Together, these findings implicate altered one-carbon metabolism as a key mechanism in photoreceptor vulnerability and adaptation in slow retinal degeneration. - Source: PubMed
Kruth KarinaBaker Sheila A - encodes Kv8.2, an electrically silent voltage-gated potassium channel subunit that is expressed in photoreceptors. Disease-causing variants in cause a monogenic disorder which is classified clinically as cone dystrophy with supernormal rod response (CDSRR). Here, we generated -deficient human retinal organoids as a tool for gene therapy vector potency assessment. The organoids were derived from two separate sources: by generating IPSCs from patient blood and by gene editing of a control cell line. Eight gene therapy vectors were assessed in retinal organoids; Kv8.2 protein levels and its in situ interactions with potassium channel binding partners were quantitatively assessed. We show significant enhancements in vector potency and specificity by transgene codon optimisation and the use of the photoreceptor-specific rhodopsin kinase (RK) promoter, respectively. Single-cell RNA sequencing was performed in transduced retinal organoids to assess the performance of the AAV vectors at single-cell resolution. -deficient photoreceptors had an upregulation in genes associated with apoptosis, oxidative stress, and hypoxia pathways which were partially restored in AAV- transduced photoreceptors. These data show how human retinal organoids can be used to evaluate AAV gene therapy vector potency in vitro in a physiologically relevant model for the selection of lead therapeutic candidates and to help minimise the use of animals in preclinical development. - Source: PubMed
Publication date: 2025/12/31
Busson Sophie LNaeem ArifaFerrara SilviaSarcar ShilpitaAdefila-Ideozu ToyinWells SarahEl Alami SophiaBoot JamesSladen Paul EMichaelides MichelGeorgiadis AnastasiosLane Amelia - - Source: PubMed
Fatihoğlu Özlem UralBozkurt Oflaz AyşeÖzkan ÖzlemTaylan Şekeroğlu HandeSaatci Ali Osman - KvS proteins are voltage-gated potassium channel subunits that form functional channels when assembled into heteromers with Kv2.1 () or Kv2.2 (). Mammals have 10 KvS subunits: Kv5.1 (), Kv6.1 (), Kv6.2 (), Kv6.3 (), Kv6.4 (), Kv8.1 (), Kv8.2 (), Kv9.1 (), Kv9.2 (), and Kv9.3 (). Electrically excitable cells broadly express channels containing Kv2 subunits and most neurons have substantial Kv2 conductance. However, whether KvS subunits contribute to these conductances has not been clear, leaving the physiological roles of KvS subunits poorly understood. Here, we identify that two potent Kv2 inhibitors, used in combination, can distinguish conductances of Kv2/KvS heteromers and Kv2-only channels. We find that Kv5, Kv6, Kv8, or Kv9-containing channels are resistant to the Kv2-selective pore-blocker RY785 yet remain sensitive to the Kv2-selective voltage sensor modulator guangxitoxin-1E (GxTX). Using these inhibitors in mouse superior cervical ganglion neurons, we find predominantly RY785-sensitive conductances consistent with channels composed entirely of Kv2 subunits. In contrast, RY785-resistant but GxTX-sensitive conductances consistent with Kv2/KvS heteromeric channels predominate in mouse and human dorsal root ganglion neurons. These results establish an approach to pharmacologically distinguish conductances of Kv2/KvS heteromers from Kv2-only channels, enabling investigation of the physiological roles of endogenous KvS subunits. These findings suggest that drugs which distinguish KvS subunits could modulate electrical activity of subsets of Kv2-expressing cell types. - Source: PubMed
Publication date: 2025/05/27
Stewart Robert GMarquis Matthew JamesJo SooyeonHarris Brandon JAberra Aman SCook VerityWhiddon ZacharyYarov-Yarovoy VladimirFerns MichaelSack Jon T - The purpose of this study was to describe a method to determine the position of the preferred retinal locus (PRL). - Source: PubMed
de Guimaraes Thales A CKalitzeos AngelosBainbridge JamesMichaelides Michel