Similar Datasets
Project description:Mutations in the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis, a pediatric neurodegenerative disorder characterized by visual loss, epilepsy and psychomotor deterioration. Although most CLN3 patients carry the same 1 kb deletion in the CLN3 gene, their disease phenotype can be variable. The aims of this study were (1) to identify genes that are dysregulated in CLN3 disease regardless of the clinical course that could be useful as biomarkers, and (2) to find modifier genes that affect the progression rate of the disease. Genome-wide expression profiling was performed in 8 CLN3 patients, homozygous for the 1 kb deletion, with different disease progression and compared to seven age and gender matched controls.
2011-06-08 | GSE22225 | GEO
Project description:Time course experiment to study the expression profile of cln3-delta bck2-delta G1 arrested yeast cells upon overexpression of CLN3
2010-06-14 | E-TABM-764 | biostudies-arrayexpress
Project description:This RNA-seq data in MNK3 cells with CRISPRi/a at CLN3 accompanies the manuscript: "High resolution promoter interaction analysis in Type 3 Innate Lymphoid Cells implicates Batten Disease gene CLN3 in Crohn's Disease aetiology".
2026-01-28 | GSE313942 | GEO
Project description:Mutations in the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis, a pediatric neurodegenerative disorder characterized by visual loss, epilepsy and psychomotor deterioration. Although most CLN3 patients carry the same 1 kb deletion in the CLN3 gene, their disease phenotype can be variable. The aims of this study were (1) to identify genes that are dysregulated in CLN3 disease regardless of the clinical course that could be useful as biomarkers, and (2) to find modifier genes that affect the progression rate of the disease. Genome-wide expression profiling was performed in 8 CLN3 patients, homozygous for the 1 kb deletion, with different disease progression and compared to seven age and gender matched controls. Lymphocytes from eight patients diagnosed with CLN3 disease,all homozygous for the 1 kb deletion in the CLN3 gene and classified as having rapid (n = 2), average (n=4), and slow disease progression (n = 2), were used. These eight patients did not receive anticonvulsive medication. In addition, lymphocytes of seven age and gender matched controls were included in the study. Lymphocytes were prepared from fresh patient blood samples by Ficoll-gradient centrifugation (BiocollM-BM-., Biochrom AG, Berlin, Germany) according to the manufacturerM-bM-^@M-^Ys protocol and used for RNA isolation (RNeasyM-BM-. Micro Kit, Qiagen, Hilden, Germany).
2011-06-08 | E-GEOD-22225 | biostudies-arrayexpress
Project description:Batten disease, one of the most devastating types of neurodegenerative lysosomal storage disorders, is caused by mutations in CLN3. Here, we show that CLN3 is a vesicular trafficking hub connecting the Golgi and lysosome compartments. Proteomic analysis reveals that CLN3 interacts with several endo-lysosomal trafficking proteins, including the cation-independent mannose 6 phosphate receptor (CI-M6PR), which coordinates the targeting of lysosomal enzymes to lysosomes. CLN3 depletion results in mis-trafficking of CI-M6PR, mis-sorting of lysosomal enzymes, and defective autophagic lysosomal reformation. Conversely, CLN3 overexpression promotes the formation of multiple lysosomal tubules, which are autophagy and CI-M6PR-dependent, generating newly formed proto-lysosomes. Together, our findings reveal that CLN3 functions as a link between the M6P-dependent trafficking of lysosomal enzymes and lysosomal reformation pathway, explaining the global impairment of lysosomal function in Batten disease.
2023-06-20 | PXD031582 | Pride
Project description:Juvenile neuronal ceroid lipofuscinoses (JNCL) is a lysosomal storage disorder associated with fatal neurodegeneration that is caused by mutations in CLN3. Most individuals with JNCL carry at least one allele with 1 kb deletion in CLN3 which results in the deletion of exons 7 and 8. There is a need for more physiologically relevant human cell-based JNCL models to better understand the cellular changes during the disease process. Using CRISPR/Cas9, we have corrected a 1 kb deletion mutation in human induced pluripotent stem cells (iPSC) of a compound heterozygous patient (CLN3 Δ1 kb and E295K), to generate an isogenic control to be used for disease modeling along with the unedited CLN3 patient iPSCs. iPSC-derived neurons carrying this particular CLN3 mutation, CLN3 neurons, had lower levels of spike, burst and network burst activity for most of the culture period. Proteomics analysis showed downregulation of proteins related to axon guidance and endocytosis on day in vitro (DIV) 14 and 42 in CLN3 neurons. This was accompanied by an increase in lysosomal-related proteins in CLN3 neurons. Western blot analysis of LAMP1 expression revealed a new finding where LAMP1 was hyperglycosylated in CLN3 neurons on DIV 14, 28 and 42, which was not apparent in control neurons. Ultrastructural analysis of CLN3 neurons showed numerous membrane-bound vacuoles containing diverse types of storage material, ranging from curvilinear deposits, multilamellar structures to osmiophilic deposits. Our findings suggest alterations in lysosomal function and neurodevelopment involving axon guidance and synaptic transmission in CLN3-deficient neuronal derivatives, which could be potential targets for therapy.
2022-12-07 | PXD032191 | Pride
Project description:This project investigated the effect of Cln3-deficiency on protein secretion in the social amoeba Dictyostelium discoideum by performing LC-MS/MS on conditioned media harvested from starved WT and cln3- cells.
2017-04-04 | PXD004897 | Pride
Project description:CLN3 is a type II transmembrane protein localized in the late endosomal/lysosomal compartment. A deficiency of CLN3 leads to the development of a certain type of Neuronal Ceroid Lipofuscinosis, a neurodegenerative disorder of childhood caused by aggregation of undegraded material in the lysosomal compartment. Cultured, immortalized wild type and Cln3(Δex7/8) cerebellar granule cells were used in this project to determine the influence of Cln3 deficiency on the proteome of the lysosomal compartment. For this purpose, cells were labelled by stable amino acid labelling in cell culture and lysosomes were isolated by magnetic beads.
2019-05-13 | PXD004548 | Pride
Project description:Loss-of-function mutations in CLN3 cause juvenile Batten disease, featuring neurodegeneration and early-stage neuroinflammation. How loss of CLN3 function leads to early neuroinflammation is not yet understood. Here, we have comprehensively studied microglia from Cln3∆ex7/8 mice, a genetically accurate disease model. Loss of CLN3 function in microglia leads to lysosomal storage material accumulation and abnormal morphology of subcellular organelles. We also discovered pathological proteomic signatures consistent with defects in lysosomal function and indicative of abnormal lipid metabolism. CLN3-deficient microglia were unable to efficiently turnover myelin and metabolize the associated lipids, showing defects in lipid droplet formation and cholesterol accumulation.
2024-10-23 | PXD048550 | Pride