Additional evidence supports GRM6 p.Thr178Met as a cause of congenital stationary night blindness in three horse breeds.
Abstract: Congenital stationary night blindness (CSNB) is an ocular disorder characterized by nyctalopia. An autosomal recessive missense mutation in glutamate metabotropic receptor 6 (GRM6 c.533C>T, p.(Thr178Met)), called CSNB2, was previously identified in one Tennessee Walking Horse and predicted to reduce binding affinity of the neurotransmitter glutamate, impacting the retinal rod ON-bipolar cell signaling pathway. Thus, the first aim was to identify the allele frequency (AF) of CSNB2 in breeds with reported cases of CSNB and breeds closely related to the Tennessee Walking Horse. The second aim was to perform ocular examinations in multiple breeds to confirm the link between genotype and CSNB phenotype. In evaluating 3518 horses from 14 breeds, the CSNB2 allele was identified in nine previously unreported breeds. The estimated AF was highest in pacing Standardbreds (0.17) and lowest in American Quarter Horses (0.0010). Complete ophthalmic examinations and electroretinograms (ERG) were performed on 19 horses from three breeds, including one CSNB2 homozygote from each breed. All three CSNB2/CSNB2 horses had an electronegative ERG waveform under scotopic light conditions consistent with CSNB. The remaining 16 horses (seven CSNB2/N and nine N/N) had normal scotopic ERG results. All horses had normal photopic ERGs. This study provides additional evidence that GRM6 c.533C>T homozygosity is likely causal to CSNB in Tennessee Walking Horses, Standardbreds, and Missouri Fox Trotting Horses. Genetic testing is recommended for breeds with the CSNB2 allele to limit the production of affected horses. This study represents the largest across-breed identification of CSNB in the horse and suggests that this disorder is likely underdiagnosed.
© 2023 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.
Publication Date: 2023-10-10 PubMed ID: 37815029DOI: 10.1111/vop.13151Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research explores the presence of a gene mutation linked to an ocular disorder known as congenital stationary night blindness (CSNB) within different horse breeds, with evidence suggesting genetic testing in affected breeds could reduce the prevalence of the condition.
Understanding Congenital Stationary Night Blindness (CSNB)
- CSNB is an eye condition that creates difficulties for horses to see in low-light or nighttime conditions. It is a genetic disorder that is present from birth and does not progress over time.
- The condition is linked to a specific gene mutation known as CSNB2, found in the glutamate metabotropic receptor 6 (GRM6). This gene mutation reduces the binding affinity of the neurotransmitter glutamate, interfering with the retinal rod ON-bipolar cell signaling pathway.
- The study aimed to ascertain the frequency of this gene mutation in different horse breeds, especially those closely related to the Tennessee Walking Horse, in which this mutation was previously identified.
Scope and Result of the Research
- The research studied 3518 horses from 14 different breeds. The CSNB2 gene mutation was found in nine of these breeds where it had not previously been identified.
- The frequency of the CSNB2 allele was found to be highest in pacing Standardbreds (0.17) and lowest in American Quarter Horses (0.0010).
- Ophthalmic examinations, including electroretinograms (ERGs), were performed on 19 horses from three different breeds: Tennessee Walking Horses, Standardbreds, and Missouri Fox Trotting Horses. All three breeds had at least one horse with two CSNB2 alleles (homozygotes) who exhibited symptoms of CSNB. Horses with either one or no CSNB2 alleles did not present these symptoms.
Implications and Recommendations
- This study offers further evidence supporting the link between the CSNB2 gene mutation and the occurrence of CSNB in horses, particularly among Tennessee Walking Horses, Standardbreds, and Missouri Fox Trotting Horses.
- The researchers recommend that genetic testing for the CSNB2 allele be carried out in breeds known to carry the allele, as this could potentially reduce the number of horses born with CSNB.
- The broad examination of different breeds in this study suggests that CSNB may be more prevalent and underdiagnosed than previously thought.
Cite This Article
APA
Esdaile E, Knickelbein KE, Donnelly CG, Ferneding M, Motta MJ, Story BD, Avila F, Finno CJ, Gilger BC, Sandmeyer L, Thomasy S, Bellone RR.
(2023).
Additional evidence supports GRM6 p.Thr178Met as a cause of congenital stationary night blindness in three horse breeds.
Vet Ophthalmol.
https://doi.org/10.1111/vop.13151 Publication
Researcher Affiliations
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, USA.
- Department of Ophthalmology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
- Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Ophthalmology & Vision Science, School of Medicine, University of California, Davis, Sacramento, California, USA.
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Grant Funding
- P30EY12576 / NEI NIH HHS
References
This article includes 27 references
- Bellone RR, Holl H, Setaluri V. Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse.. PLoS One 2013;8(10):e78280.
- Zeitz C, Robson AG, Audo I. Congenital stationary night blindness: an analysis and update of genotype-phenotype correlations and pathogenic mechanisms.. Prog Retin Eye Res 2015;45:58-110.
- Hack YL, Crabtree EE, Avila F. Whole-genome sequencing identifies missense mutation in GRM6 as the likely cause of congenital stationary night blindness in a Tennessee Walking Horse.. Equine Vet J 2021;53(2):316-323.
- Križaj D, Cordeiro S, Strauß O. Retinal TRP channels: cell-type-specific regulators of retinal homeostasis and multimodal integration.. Prog Retin Eye Res 2023;92:101114.
- Bellone RR, Brooks SA, Sandmeyer L. Differential gene expression of TRPM1, the potential cause of congenital stationary night blindness and coat spotting patterns (LP) in the Appaloosa horse (Equus caballus).. Genetics 2008;179(4):1861-1870.
- Sandmeyer LS, Bellone RR, Archer S. Congenital stationary night blindness is associated with the leopard complex in the Miniature horse.. Vet Ophthalmol 2012;15(1):18-22.
- Nunnery C, Pickett JP, Zimmerman KL. Congenital stationary night blindness in a thoroughbred and a Paso Fino.. Vet Ophthalmol 2005;8(6):415-419.
- Rebhun WC. Retinal and optic nerve diseases.. Vet Clin North Am Equine Pract 1992;8(3):587-608.
- Kirk NG. Congenital and acquired ophthalmic diseases in the foal.. Animal Eye Research 1993;12(1-2):15-27.
- Petersen JL, Mickelson JR, Cothran EG. Genetic diversity in the modern horse illustrated from genome-wide SNP data.. PLoS One 2013;8(1):e54997.
- Gorman JA. The Western Horse, its types and training.. The Interstate 1949.
- Cothran EG, Autry S. Analysis of genetic variation in the Rocky Mountain horse.. Rocky Mountain Horse Association 2015:17.
- Guest K, Mattfeld M. Equestrian cultures: horses, human society, and the discourse of modernity (animal lives).. Vol 282. University of Chicago Press; 2019.
- . History of the Missouri Fox Trotter.. Missouri Fox Trotting Horse Breed Association 2019.
- . Racking Horse Breeders Association of America.. Accessed March 1, 2023.
- . About|National Spotted Saddle Horse Association.. Accessed March 1, 2023.
- Elcombe ME, Bellone RR, Magdesian KG, Finno CJ. Prevalence of the RAPGEF5 c.2624C>A and PLOD1 c.2032G>A variants associated with equine familial isolated hypoparathyroidism and fragile foal syndrome in the US thoroughbred population (1988-2019).. Equine Vet J 2022;5:666-671.
- Locke MM, Penedo MCT, Bricker SJ, Millon LV, Murray JD. Linkage of the grey coat colour locus to microsatellites on horse chromosome 25.. Anim Genet 2002;33(5):329-337.
- Toro S, Matentzoglu NA, Vasilevsky NA, Mullen KR. Monarch-initiative/vertebrate-breed-ontology: v2023-06-01.. Zenodo 2023.
- Esdaile E, Avila F, Bellone RR. Analysis of genetic diversity in the American Standardbred horse utilizing short tandem repeats and single nucleotide polymorphisms.. J Hered 2022;113(3):238-247.
- . Confidence interval of a proportion.. Accessed March 7, 2023.
- Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis.. Nat Methods 2012;9(7):671-675.
- . Official 2023 rulebook.. The American Miniature Horse Association Inc. 2023, B-21.
- Denzel A, Molinari M, Trigueros C. Early postnatal death and motor disorders in mice congenitally deficient in calnexin expression.. Mol Cell Biol 2002;22(21):7398-7404.
- Kraus A, Groenendyk J, Bedard K. Calnexin deficiency leads to dysmyelination.. J Biol Chem 2010;285(24):18928-18938.
- Glynn D, Bortnick RA, Morton AJ. Complexin II is essential for normal neurological function in mice.. Hum Mol Genet 2003;12(19):2431-2448.
- AXCIS Information Network, Inc. TrackMaster Horse Ratings.. TrackMaster, an Equibase Company 2023.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
