Evidence map›Paper›PMID 39737777›Full record

ArticleGenetics2025

A Drosophila model of mucopolysaccharidosis IIIB.

Bibhu Simkhada, Nestor O Nazario-Yepiz, Patrick S Freymuth, Rachel A Lyman, Vijay Shankar, Kali Wiggins, Heather Flanagan-Steet, Amrita Basu, Ryan J Weiss, Robert R H Anholt and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Bibhu SimkhadaDepartment of Genetics and Biochemistry and Center for Human Genetics, Clemson University, 114 Gregor Mendel Circle, Greenwood, SC 29646, USA.
Nestor O Nazario-YepizDepartment of Genetics and Biochemistry and Center for Human Genetics, Clemson University, 114 Gregor Mendel Circle, Greenwood, SC 29646, USA.
Patrick S FreymuthDepartment of Genetics and Biochemistry and Center for Human Genetics, Clemson University, 114 Gregor Mendel Circle, Greenwood, SC 29646, USA.
Rachel A LymanDepartment of Genetics and Biochemistry and Center for Human Genetics, Clemson University, 114 Gregor Mendel Circle, Greenwood, SC 29646, USA.
Vijay ShankarDepartment of Genetics and Biochemistry and Center for Human Genetics, Clemson University, 114 Gregor Mendel Circle, Greenwood, SC 29646, USA.
Kali WigginsGreenwood Genetic Center, JC Self Research Institute, 106 Gregor Mendel Circle, Greenwood, SC 29646, USA.
Heather Flanagan-SteetGreenwood Genetic Center, JC Self Research Institute, 106 Gregor Mendel Circle, Greenwood, SC 29646, USA.
Amrita BasuComplex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
Ryan J WeissComplex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.ORCID 0000-0002-4563-6075
Robert R H AnholtDepartment of Genetics and Biochemistry and Center for Human Genetics, Clemson University, 114 Gregor Mendel Circle, Greenwood, SC 29646, USA.ORCID 0000-0001-7196-8324
Trudy F C MackayDepartment of Genetics and Biochemistry and Center for Human Genetics, Clemson University, 114 Gregor Mendel Circle, Greenwood, SC 29646, USA.ORCID 0000-0002-2312-7245

Funding

Statistical Methods for Gene Regulatory Analysis From Single Cell Genomics DataP20GM139769 · NIGMS · CLEMSON UNIVERSITY · PI ANHOLT, ROBERT R. H, ARNO, GAVIN · 2021 to 2025
$10.8M
National Glycoscience Resource- CCRC Service and Training - NGlycoR@CCRCR24GM137782 · NIGMS · UNIVERSITY OF GEORGIA · PI Parastoo Azadi · 2020 to 2026
$5.2M
Investigating the molecular mechanisms of glycosaminoglycan assemblyR35GM150736 · NIGMS · UNIVERSITY OF GEORGIA · PI Ryan Joseph Weiss · 2023 to 2026
$1.5M
Cure Sanfilippo FoundationGenomics and Statistics and Bioinformatics Research CoreNIGMS NIH HHS P20 GM139769NIGMS NIH HHS R24 GM137782NIGMS NIH HHS R35 GM150736NIH HHS R24GM137782WellGenetics
6 · The paper itself

Abstract

Mucopolysaccharidosis type IIIB is a rare lysosomal storage disorder caused by defects in alpha-N-acetylglucosaminidase (NAGLU) and characterized by severe effects in the central nervous system. Mutations in NAGLU cause accumulation of partially degraded heparan sulfate in lysosomes. The consequences of these mutations on whole-genome gene expression and their causal relationships to neural degeneration remain unknown. Here, we used the functional Drosophila melanogaster ortholog of NAGLU, Naglu, to develop a fly model for MPS IIIB induced by gene deletion (NagluKO), missense (NagluY160C), and nonsense (NagluW422X) mutations. We used the Drosophila activity monitoring system to analyze activity and sleep and found sex- and age-dependent hyperactivity and sleep defects in mutant flies. Fluorescence microscopy on mutant fly brains using Lysotracker dye revealed a significant increase in acidic compartments. Differentially expressed genes determined from RNA sequencing of fly brains are involved in biological processes that affect nervous system development. A genetic interaction network constructed using known interacting partners of these genes consists of 2 major subnetworks, one of which is enriched in genes associated with synaptic function and the other with neurodevelopmental processes. Our data indicate that lysosomal dysfunction arising from disruption of heparan sulfate breakdown has widespread effects on the steady state of intracellular vesicle transport, including vesicles associated with synaptic transmission. Evolutionary conservation of fundamental biological processes predicts that the Drosophila model of mucopolysaccharidosis type IIIB can serve as an in vivo system for the future development of therapies for mucopolysaccharidosis type IIIB and related disorders.

Indexed as

AcetylglucosaminidaseDisease Models, AnimalDrosophila melanogasterMucopolysaccharidosis IIIAnimalsBrainDrosophila ProteinsFemaleHeparan SulfateLysosomesMaleMutationAcetylglucosaminidasealpha-N-acetyl-D-glucosaminidaseDrosophila ProteinsHeparan Sulfatelysosomal storage disorderNAGLUrare genetic diseaseRNA sequencingSanfilippo syndromesleep fragmentationtranscriptomics

Identifiers

PMID39737777
PMCPMC11912869

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.