{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T05:18:36Z","timestamp":1763011116220,"version":"3.45.0"},"reference-count":75,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"crossref","award":["S10 OD032246","EY031674"],"award-info":[{"award-number":["S10 OD032246","EY031674"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Orthopedic Foundation for Animals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: A Petit Bleu de Gascogne (PBDG) dog presented with a progressive neurological disorder characterized by hind-limb weakness, anxiety and hallucinatory episodes, lip smacking, progressive vision loss, muscle atrophy, and ataxia. Magnetic resonance imaging revealed diffuse brain atrophy. The dog was euthanized at approximately 23 months of age due to the progression of neurological signs. A study was undertaken to identify the molecular genetic basis of the disorder in this dog. Methods: Microscopic analyses were performed to characterize the disease pathology and whole-genome sequencing was performed to identify the molecular genetic basis of the disorder. Results: The proband exhibited pronounced accumulations of autofluorescent intracellular inclusions in the brain, retina, and heart with ultrastructural appearances similar to those of lysosomal storage bodies that accumulate in the neuronal ceroid lipofuscinosis (NCLs), a group of progressive neurodegenerative disorders. Whole-genome sequence analysis of DNA from the proband identified homozygous missense variants in AP3B1 and TRAPPC9 that encode proteins involved in sorting and transport of proteins through the Golgi apparatus to lysosomes. Screening of unaffected PBDGs for these variants identified dogs that were homozygous for either variant, but no other dogs that were homozygous for both. Conclusions: These findings raise the possibility that the disease involves the combined influence of the two variants, and that the proteins encoded by these genes interact within the Golgi apparatus to mediate protein sorting and transport to lysosomes. An alteration in this interaction could underlie the NCL-like lysosomal storage disorder observed in the proband.<\/jats:p>","DOI":"10.3390\/genes16111370","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:56:27Z","timestamp":1762858587000},"page":"1370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Canine Neuronal Ceroid Lipofuscinosis-like Disorder Associated with Sequence Variants in AP3B1 and TRAPPC9"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9406-4296","authenticated-orcid":false,"given":"Alexander","family":"Then","sequence":"first","affiliation":[{"name":"Bl\u00e5 Stj\u00e4rnans Djursjukhus, SE-43137 M\u00f6lndal, Sweden"},{"name":"Faculty of Medicine and Health, School of Medical Sciences, \u00d6rebro University, SE-70182 \u00d6rebro, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9277-3675","authenticated-orcid":false,"given":"Rebecca","family":"Welly","sequence":"additional","affiliation":[{"name":"Canine Genetics Laboratory, Department of Veterinary Pathobiology and Integrative Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-8758","authenticated-orcid":false,"given":"Garrett","family":"Bullock","sequence":"additional","affiliation":[{"name":"Canine Genetics Laboratory, Department of Veterinary Pathobiology and Integrative Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8602-1993","authenticated-orcid":false,"given":"Lucie","family":"Chevallier","sequence":"additional","affiliation":[{"name":"U955\u2014IMRB, Team 10\u2014Biology of the Neuromuscular System, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, 94704 Maisons-Alfort, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2582-9187","authenticated-orcid":false,"given":"Martin L.","family":"Katz","sequence":"additional","affiliation":[{"name":"Canine Genetics Laboratory, Department of Veterinary Pathobiology and Integrative Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.nbd.2017.08.017","article-title":"Canine Neuronal Ceroid Lipofuscinoses: Promising Models for Preclinical Testing of Therapeutic Interventions","volume":"108","author":"Katz","year":"2017","journal-title":"Neurobiol. 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