Selected Grantee Publications
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- 4 results found
- Other Animal Models
- Genetics
- 2023
Global Frequency Analyses of Canine Progressive Rod-Cone Degeneration-Progressive Retinal Atrophy and Collie Eye Anomaly Using Commercial Genetic Testing Data
Clark et al., Genes (Basel). 2023.
https://pubmed.ncbi.nlm.nih.gov/38003037/
Hundreds of genetic variants associated with canine traits and disorders have been identified; however, the geographic distributions and changes in allele and genotype frequencies over prolonged, continuous periods of time are lacking. This study utilized a large set of genotypes from dogs tested for progressive rod-cone degeneration-progressive retinal atrophy (prcd‑PRA) and collie eye anomaly (CEA). Both diseases exhibited significant differences in genotype frequencies (p=2.7 × 10-152 for prcd-PRA and 0.023 for CEA) with opposing graphical trends. This study shows that genetic testing informed breeding decisions to produce fewer affected dogs. Supported by ORIP (K01OD027051).
A SACS Deletion Variant in Great Pyrenees Dogs Causes Autosomal Recessive Neuronal Degeneration
Ekenstedt et al., Human Genetics. 2023.
https://pubmed.ncbi.nlm.nih.gov/37758910/
ARSACS (autosomal recessive spastic ataxia of Charlevoix-Saguenay) is an early-onset, slowly progressive neurodegenerative disorder. To date, no naturally occurring large animal model has been reported for ARSACS. In this study, the authors describe a novel spontaneous genetic model for SACS-associated neuronal degeneration using Great Pyrenees dogs of both sexes. The canine models described in this study fit closely with the typical early‑onset ARSACS phenotype in humans, and molecular genetic studies demonstrated that these dogs exhibit a deleterious SACS mutation. The clinical and histopathological descriptions of this canine disorder contribute to the description of human ARSACS. Supported by ORIP (R01OD01027051).
Canine Models of Charcot-Marie-Tooth: MTMR2, MPZ, and SH3TC2 Variants in Golden Retrievers With Congenital Hypomyelinating Polyneuropathy
Cook et al., Neuromuscular Disorders. 2023.
https://pubmed.ncbi.nlm.nih.gov/37400349/
Both demyelination and hypomyelination of the nervous system are associated with various clinical diseases. Using whole-genome sequencing, researchers determined the genetic underpinnings of congenital hypomyelinating polyneuropathy in canines of both sexes. These variants genetically describe the first peripheral nervous system–exclusive hypomyelinating polyneuropathies in dogs. By testing for these mutations, breeders can prevent the production of affected offspring. Supported by ORIP (K01OD027051, K01OD027058).
Effect of the Snake Venom Component Crotamine on Lymphatic Endothelial Cell Responses and Lymph Transport
Si et al., Microcirculation. 2023.
https://onlinelibrary.wiley.com/doi/10.1111/micc.12775
The pathology of snake envenomation is closely tied to the severity of edema in the tissue surrounding the area of the bite. This study focused on one of the most abundant venom components in North American viper venom, crotamine, and the effects it has on the cells and function of the lymphatic system. The authors found that genes that encode targets of crotamine are highly present in lymphatic tissues and cells and that there is a differential distribution of those genes that correlates with phasic contractile activity. They found that crotamine potentiates calcium flux in human dermal lymphatic endothelial cells in response to stimulation with histamine and shear stress—but not alone—and that it alters the production of nitric oxide in response to shear, as well as changes the level of F-actin polymerization of those same cells. Crotamine alters lymphatic transport of large molecular weight tracers to local lymph nodes and is deposited within the node, mostly in the immediate subcapsular region. Results suggest that snake venom components may have an impact on the function of the lymphatic system and provide new targets for improved therapeutics to treat snakebites. Supported by ORIP (P40OD010960).