Schwarz, Cleo Georgette (2024). Canine RNF170 Single Base Deletion in a Naturally Occurring Model for Human Neuroaxonal Dystrophy. (Thesis). Universität Bern, Bern
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Abstract
Neuroaxonal dystrophy (NAD) is a group of inherited neurodegenerative disorders characterized primarily by the presence of spheroids (swollen axons) throughout the central nervous system. In humans, NAD is heterogeneous, both clinically and genetically. NAD has also been reported to naturally occur in large animal models, such as dogs. This study describes a newly recognized disorder in Miniature American Shepherd dogs (MAS), consisting of slowly progressive neurodegenerative signs, that was diagnosed as NAD via histopathology. Affected dogs were typically young adults and displayed an abnormal gait characterized by pelvic limb weakness and ataxia. A genomewide association study and autozygosity mapping approach, followed by whole-genome sequencing, identified a 1-base-pair deletion in RNF170 as the underlying genetic cause. This deletion is predicted to create a frameshift (XM_038559916.1:c.367delG) and early truncation of the RNF170 protein (XP_038415844.1:(p.Ala123Glnfs*11)) and perfectly segregates in an autosomal recessive pattern. RNF170 variants were previously identified in human patients with autosomal recessive spastic paraplegia-85; this clinical phenotype shows similarities to the dogs described herein. We therefore propose that this novel MAS NAD could serve as an excellent large animal model for equivalent human diseases, particularly since affected dogs demonstrate a relatively long lifespan, which represents an opportunity for therapeutic trials.
| Item Type: | Thesis |
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| Dissertation Type: | Single |
| Date of Defense: | 8 October 2024 |
| Subjects: | 500 Science > 590 Animals (Zoology) 600 Technology > 630 Agriculture |
| Institute / Center: | 05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics |
| Depositing User: | Hammer Igor |
| Date Deposited: | 17 Apr 2025 13:42 |
| Last Modified: | 17 Apr 2025 14:09 |
| URI: | https://boristheses.unibe.ch/id/eprint/6000 |
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