AI Article Synopsis

  • Genetic Leukoencephalopathies (gLEs) are inherited disorders affecting white matter and leading to neurological issues, with a specific mutation in VPS11 identified in Ashkenazi Jewish individuals.
  • Researchers analyzed the visual and sensorimotor capabilities in zebrafish mutant lines (vps11(plt) and vps11(-/-)) to assess their responses to light and sound.
  • The study revealed that both mutant zebrafish exhibited impaired visual and sensorimotor responses, particularly as they matured, establishing a model for further pharmacological research on gLE treatments.

Article Abstract

Genetic Leukoencephalopathies (gLEs) are heritable white matter disorders that cause progressive neurological abnormalities. A founder mutation in the human endolysosomal trafficking protein VPS11 has been identified in Ashkenazi Jewish patients manifesting classic gLE symptoms of hypomyelination, developmental delay, motor and systemic deficits. In this study, we characterized the visual and sensorimotor function of two zebrafish vps11 mutant lines: the previously reported vps11(plt), and a new vps11(-/-) null mutant line, using behavioral analysis to track larval motor responses to visual and acoustic stimuli. We found that mutant larvae from both vps11(plt) and vps11(-/-) lines were able to visually distinguish light and dark, but showed a progressive loss of a normal sensorimotor response to visual stimuli from 5 days post fertilization (dpf) to 7dpf. Additionally, optokinetic response analysis performed at 5dpf indicated that the mutants were significantly visually impaired. Both mutant lines also displayed a progressively lower sensorimotor response to a singular acoustic stimulus from 5-7dpf. Next, we tested the habituation response of the mutant lines to series of acoustic taps. We found both mutant lines habituated faster than their siblings, and that vps11(plt) mutants habituated faster than the vps11(-/-) mutants. Together, these data suggest that loss of Vps11 function results in progressive visual and sensorimotor abnormalities in the zebrafish vps11(plt) and vps11(-/-) mutant lines. This is the first study to characterize behavioral deficits in a vertebrate model of Vps11-dependent gLE. The mutants and behavioral assays described here could be a valuable model system in which to test potential pharmacological interventions for gLE.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894412PMC
http://dx.doi.org/10.1038/s41598-022-07448-1DOI Listing

Publication Analysis

Top Keywords

mutant lines
20
vps11plt vps11-/-
12
loss vps11
8
vps11 function
8
function zebrafish
8
visual sensorimotor
8
sensorimotor response
8
habituated faster
8
mutant
7
lines
6

Similar Publications

Background: KRAS inhibitors are revolutionizing the treatment of NSCLC, but clinico-genomic determinants of treatment efficacy warrant continued exploration.

Methods: Patients with advanced KRASG12C-mutant NSCLC treated with adagrasib (KRYSTAL-1-NCT03785249) were included in the analysis. Pre-treatment NGS data were collected per protocol.

View Article and Find Full Text PDF

MaGA20ox2f, an OsSD1 homolog, regulates flowering time and fruit yield in banana.

Mol Breed

January 2025

Institute of Fruit Tree Research, Key Laboratory of South Subtropical Fruit Biology and Genetic Resource Utilization, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Science and Technology Research On Fruit Tree, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640 Guangdong China.

Unlabelled: Previous studies illustrated that two banana GA20 oxidase2 (MaGA20ox2) genes, and , are implicated in controlling banana growth and development; however, the biological function of each gene remains unknown. Ma04g15900 protein (termed MaGA20ox2f in this article) is the closest homolog to the Rice SD1 (encoded by 'green revolution gene', ) in the banana genome. The expression of is confined to leaves, peduncles, fruit peels, and pulp.

View Article and Find Full Text PDF

Resveratrol is an important phytoalexin that adapts to and responds to stressful conditions and plays various roles in health and medical therapies. However, it is only found in a limited number of plant species in low concentrations, which hinders its development and utilization. Chalcone synthase (CHS) and stilbene synthase (STS) catalyze the same substrates to produce flavonoids and resveratrol, respectively.

View Article and Find Full Text PDF

An endoplasmic reticulum-localized Cu transporter, PhHMA5II1, interacts with copper chaperones and plays an important role in Cu detoxification in petunia. Copper (Cu) is an essential element for plant growth but toxic when present in excess. In this study we present the functional characterization of a petunia (Petunia hybrida) P-type heavy-metal ATPases (HMAs), PhHMA5II1.

View Article and Find Full Text PDF

Background: Mutations in the structural domain of the epidermal growth factor receptor (EGFR) kinase represent a critical pathogenetic factor in non-small cell lung cancer (NSCLC). Small-molecule EGFR-tyrosine kinase inhibitors (TKIs) serve as first-line therapeutic agents for the treatment of EGFR-mutated NSCLC. But the resistance mutations of EGFR restrict the clinical application of EGFR-TKIs.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!