{"topic_id":"companion_species_health_neuronal_ceroid_lipofuscinosis_2_dog","category":"companion-species-health","context":"---\nlicense: permission_granted\ntopic_id: companion_species_health_neuronal_ceroid_lipofuscinosis_2_dog\ncategory: companion-species-health\ntitle: \"Dog (Canis lupus familiaris) — Neuronal ceroid lipofuscinosis, 2 (hereditary; OMIA-verified species predisposition)\"\nlang: en\nsource: \"OMIA (Online Mendelian Inheritance in Animals, University of Sydney) species-specific hereditary-disorder record, saved verbatim to source_file; C1 substring-verified. Pulled 2026-08-24 from local OMIA database dump.\"\nsource_file: pdf-raw/species-health/dog_neuronal_ceroid_lipofuscinosis_2_2901.txt\ndate_parsed: 2026-08-24\ntokens_estimated: 922\nverification:\n  method: substring_match\n  claims: 8\n  passed: 8\n  date: 2026-08-24\nrecovered: false\npath: companion-species-health/companion_species_health_neuronal_ceroid_lipofuscinosis_2_dog/01_companion_species_health_neuronal_ceroid_lipofuscinosis_2_dog.md\nsource_document: \"OMIA — Online Mendelian Inheritance in Animals (University of Sydney)\"\ncitation:\n  authority: \"OMIA — Online Mendelian Inheritance in Animals (University of Sydney)\"\n  title: \"Dog (Canis lupus familiaris) — Neuronal ceroid lipofuscinosis, 2 (hereditary; OMIA-verified species predisposition)\"\n  url: \"https://omia.org/OMIA001472/9615/\"\n  retrieved: \"2026-08-24\"\n  ref: \"OMIA species-specific hereditary-disorder records (omia.org), derived from local OMIA database dump; dataset: https://doi.org/10.25910/2AMR-PV70\"\n  doc_type: \"academic animal-genetics database (species-specific disorder entries)\"\n  needs_review: false\n\nverification_derived:\n  method: derived_from_dataset\n  source: \"OMIA database dump (omia.xml, local); fields Gene/Variant/Article/OMIM\"\n  note: \"Structured fields (gene, variant rsID/protein change, PubMed/DOI references, OMIM cross-link) extracted from OMIA dump and presented with first-hand values; not verbatim prose.\"---\n\n# Dog (Canis lupus familiaris) — Neuronal ceroid lipofuscinosis, 2 (hereditary; OMIA-verified species predisposition)\n\nSource: first-hand OMIA (University of Sydney) species-specific hereditary-disorder record, saved verbatim to `source_file`; every claim below is a C1 byte-substring of it.\n\n## Claims\n\n- `Species: Dog (Canis lupus familiaris)`\n- `Disorder: Neuronal ceroid lipofuscinosis, 2`\n- `Summary: The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases characterized by intraneuronal accumulation of fluorescent granules, early neuronal death, and progressive neurodegeneration of the central nervous system. NCL2 is an early-onset disease of miniature long-haired dachshunds. Early signs include progressive loss of vision under dim light, decreased menace response, tremors of the head, myoclonus, and cerebellar ataxia. Signs appear in young dogs and progress rapidly, with death by 12 months of age., as no effective treatment has been identified. The mode of inheritance is autosomal recessive. Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT Kick et al. (2023) \"A study using the dog model was performed to evaluate the efficacy of ocular gene therapy to provide a continuous, long-term source of human TPP1 (hTPP1) to the retina, inhibit retinal degeneration and preserve retinal function. ... Intravitreal administration of AAV2.CAG.hTPP1 resulted in stable, widespread expression of hTPP1 throughout the inner retina, prevented disease-related declines in retinal function and inhibited disease-related cell loss and storage body accumulation in the retina for at least 6 months. Uveitis occurred in eyes treated with the hTPP1 vector, but this did not prevent therapeutic efficacy.\"`\n- `Clin feat: Progressive loss of vision under dim light begins in affected dogs at 6-7 months of age (Sanders et al., 2011). Unilaterally decreased menace response begins at 8 months of age, followed by intention and resting tremors of the head, and myoclonus. Cerebellar ataxia (dysmetria, incoordination) began at 9-10 months of age. Other neurological signs include altered cognitive function, motor dysfunction, and myoclonus. Tests of cognitive ability were significantly different from normal dogs at 6 months of age (Sanders et al., 2011). Other signs reported include seizures, hyperactivity, howling, aggressive behavior, hypermetria, circling, and diarrhea (Awano et al., 2006). No effective treatment has been identified, and affected dogs die by 12 months of age (Awano et al., 2006). Intrathecal administration of TPP1 caused a robust immune response and did not improve the overall function of treated dogs (Vuillemenot et al., 2011).`\n- `Pathology: Affected dogs have less than 1% TPP1 activity in the cerebral cortex (Awano et al., 2006). Autofluorescent lysosomal storage occurs throughout the central nervous system. Some cerebral cortex cells have large storage bodies, but most have little to none. Storage material is present in all layers of the cerebellum, but only moderate in Purkinje cells. In the spinal cord, most autofluorescent storage is in large motor neurons. Curvilinear aggregates in the lysosomes are identified by electron microscopy (Awano et al., 2006, Vuillemenot et al., 2011). Histopathology of the cerebellum includes white matter depletion, decreased numbers of cortical neurons, a narrowed molecular layer, a sparsely populated internal granular layer, and irregularly spaced Purkinje cells. Larger neurons in the cerebrum and spinal cord contain coarse eosinophilic, PAS positive cytoplasmic granules (Awano et al., 2006).`\n- `Prevalence: The mutation appears to be uncommon among miniature long-haired dachshunds (Awano et al., 2006).`\n- `Control: Parents of affected dogs are obligate carriers. Siblings of affected animals should be tested. Breeding of affected or carrier dogs is not recommended.`\n- `Gen test: A test is available to detect the causative mutation in miniature long-haired dachshunds.`\n## Associated gene(s)\nDerived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.\n- Gene: CLN2 (Entrez Gene ID 485337) — OMIA Phene_Gene / GeneSynonym\n- OMIA molecular-genetics note: The causative mutation is a single nucleotide deletion (c.325delC) in exon 4 of TPP1, which causes an amino acid codon frameshift and a premature stop codon (Awano et al., 2006). There is an analogous disease in humans (OMIM# 204500).\n\n## Evidence (references)\nDerived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.\n- 2006. A frame shift mutation in canine TPP1 (the ortholog of human CLN2) in a juvenile Dachshund with neuronal ceroid lipofuscinosis. Mol Genet Metab — PubMed:PMID16621647 | DOI:10.1016/j.ymgme.2006.02.016 — OMIA Phene_Article / Article\n- 2011. Intrathecal tripeptidyl-peptidase 1 reduces lysosomal storage in a canine model of late infantile neuronal ceroid lipofuscinosis. Mol Genet Metab — PubMed:PMID21784683 | DOI:10.1016/j.ymgme.2011.06.018 — OMIA Phene_Article / Article\n- 2011. A reversal learning task detects cognitive deficits in a Dachshund model of late-infantile neuronal ceroid lipofuscinosis. Genes Brain Behav — PubMed:PMID21745338 | DOI:10.1111/j.1601-183X.2011.00718.x — OMIA Phene_Article / Article\n- 2013. Use of model organisms for the study of neuronal ceroid lipofuscinosis. Biochim Biophys Acta — PubMed:PMID23338040 | DOI:10.1016/j.bbadis.2013.01.009 — OMIA Phene_Article / Article\n- 2008. Retinal pathology in a canine model of late infantile neuronal ceroid lipofuscinosis. Invest Ophthalmol Vis Sci — PubMed:PMID18344450 | DOI:10.1167/iovs.08-1712 — OMIA Phene_Article / Article\n- 2013. Pupillary light reflex deficits in a canine model of late infantile neuronal ceroid lipofuscinosis. Exp Eye Res — PubMed:PMID24135299 | DOI:10.1016/j.exer.2013.10.006 — OMIA Phene_Article / Article\n- 2015. Multifocal retinopathy in Dachshunds with CLN2 neuronal ceroid lipofuscinosis. Exp Eye Res — PubMed:PMID25697710 | DOI:10.1016/j.exer.2015.02.012 — OMIA Phene_Article / Article\n- 2014. Enzyme replacement therapy delays pupillary light reflex deficits in a canine model of late infantile neuronal ceroid lipofuscinosis. Exp Eye Res — PubMed:PMID24954537 | DOI:10.1016/j.exer.2014.06.008 — OMIA Phene_Article / Article\n- 2016. Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease. Exp Eye Res — PubMed:PMID27039708 | DOI:10.1016/j.exer.2016.03.023 — OMIA Phene_Article / Article\n- 2015. AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease. Sci Transl Med — PubMed:PMID26560358 | DOI:10.1126/scitranslmed.aac6191 — OMIA Phene_Article / Article\n- 2016. Intravitreal implantation of TPP1-transduced stem cells delays retinal degeneration in canine CLN2 neuronal ceroid lipofuscinosis. Exp Eye Res — PubMed:PMID27637672 | DOI:10.1016/j.exer.2016.09.003 — OMIA Phene_Article / Article\n- 2016. CLN2 Disease (Classic Late Infantile Neuronal Ceroid Lipofuscinosis). Pediatr Endocrinol Rev — PubMed:PMID27491216 — OMIA Phene_Article / Article\n- (15 additional references in OMIA)\n\n## Comparative medicine (human OMIM)\nDerived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.\n- OMIM:204500 (type: trait) — OMIA Group_OMIM (via OMIA_ID)\n- OMIM:607998 (type: gene) — OMIA Group_OMIM (via OMIA_ID)\n- OMIM:609270 (type: trait) — OMIA Group_OMIM (via OMIA_ID)\n","sources":["companion-species-health — Dog (Canis lupus familiaris) — Neuronal ceroid lipofuscinosis, 2 (hereditary; OMIA-verified species predisposition)"],"source":{"authority":"companion-species-health","title":"Dog (Canis lupus familiaris) — Neuronal ceroid lipofuscinosis, 2 (hereditary; OMIA-verified species predisposition)","url":"https://pubmed.ncbi.nlm.nih.gov/16621647/","retrieved":"","ref":"PMID 16621647","doc_type":"official source","source_document":"","verification_file":""},"source_document":"","source_file":"","trust":{"authority_tier":"ungraded","fidelity":"verbatim","license":null,"display_grade":"pending"},"tokens_estimated":1640,"generated_at":null,"tip":"Use /api/v1/topics to discover more topics. /api/v1/nutrient for precise single-point queries. /api/v1/cross_compare for 2-3 standard comparisons."}