{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mikulka CR"],"funding":["HHS | National Institutes of Health","BioMarin Pharmaceutical","NIA NIH HHS","NINDS NIH HHS"],"pagination":["9032-9041"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7183170"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["117(16)"],"pubmed_abstract":["Lysosomal storage diseases (LSDs) are typically caused by a deficiency in a soluble acid hydrolase and are characterized by the accumulation of undegraded substrates in the lysosome. Determining the role of specific cell types in the pathogenesis of LSDs is a major challenge due to the secretion and subsequent uptake of lysosomal hydrolases by adjacent cells, often referred to as \"cross-correction.\" Here we create and validate a conditional mouse model for cell-autonomous expression of galactocerebrosidase (GALC), the lysosomal enzyme deficient in Krabbe disease. We show that lysosomal membrane-tethered GALC (GALCLAMP1) retains enzyme activity, is able to cleave galactosylsphingosine, and is unable to cross-correct. Ubiquitous expression of GALCLAMP1 fully rescues the phenotype of the GALC"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Cell-autonomous expression of the acid hydrolase galactocerebrosidase."],"pmcid":["PMC7183170"],"funding_grant_id":["1","NS100779","R01 NS100779","R01 NS087632","R01 AG013730","RF1 AG013730"],"pubmed_authors":["Benitez BA","Milbrandt J","Liu L","Mikulka CR","Strickland A","Dearborn JT","Sands MS"],"additional_accession":[]},"is_claimable":false,"name":"Cell-autonomous expression of the acid hydrolase galactocerebrosidase.","description":"Lysosomal storage diseases (LSDs) are typically caused by a deficiency in a soluble acid hydrolase and are characterized by the accumulation of undegraded substrates in the lysosome. Determining the role of specific cell types in the pathogenesis of LSDs is a major challenge due to the secretion and subsequent uptake of lysosomal hydrolases by adjacent cells, often referred to as \"cross-correction.\" Here we create and validate a conditional mouse model for cell-autonomous expression of galactocerebrosidase (GALC), the lysosomal enzyme deficient in Krabbe disease. We show that lysosomal membrane-tethered GALC (GALCLAMP1) retains enzyme activity, is able to cleave galactosylsphingosine, and is unable to cross-correct. Ubiquitous expression of GALCLAMP1 fully rescues the phenotype of the GALC","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Apr","modification":"2025-06-01T12:02:28.887Z","creation":"2025-06-01T12:02:28.887Z"},"accession":"S-EPMC7183170","cross_references":{"pubmed":["32253319"],"doi":["10.1073/pnas.1917675117"]}}