Congenital stationary night blindness is associated with the leopard complex in the Miniature Horse.

OBJECTIVE   To determine if congenital stationary night blindness (CSNB) exists in the Miniature Horse in association with leopard complex spotting patterns (LP), and to investigate if CSNB in the Miniature Horse is associated with three single nucleotide polymorphisms (SNPs) in the region of TRPM1 that are highly associated with CSNB and LP in Appaloosas. ANIMALS STUDIED   Three groups of Miniature Horses were studied based on coat patterns suggestive of LP/LP (n=3), LP/lp (n=4), and lp/lp genotype (n=4). PROCEDURES   Horses were categorized based on phenotype as well as pedigree analysis as LP/LP, LP/lp, and lp/lp. Neurophthalmic examination, slit-lamp biomicroscopy, indirect ophthalmoscopy, and scotopic flash electroretinography were performed on all horses. Hair samples were processed for DNA analysis. Three SNPs identified and associated with LP and CSNB in the Appaloosa were investigated for association with LP and CSNB in these Miniature Horses. RESULTS   All horses in the LP/LP group were affected by CSNB, while none in the LP/lp or lp/lp groups were affected. All three SNPs were completely associated with LP genotype (χ(2) = 22, P << 0.0005) and CSNB status (χ(2) =11, P<0.0005). CONCLUSIONS   The Miniature Horse breed is affected by CSNB and it appears to be associated with LP as in the Appaloosa breed. The SNPs tested could be used as a DNA test for CSNB until the causative mutation is determined.

[1]  C. Wade,et al.  Association analysis of candidate SNPs in TRPM1 with leopard complex spotting (LP ) and congenital stationary night blindness (CSNB) in horses , 2010 .

[2]  P. Sieving,et al.  A mutation in SLC24A1 implicated in autosomal-recessive congenital stationary night blindness. , 2010, American journal of human genetics.

[3]  Hiroshi Ueda,et al.  TRPM1: a vertebrate TRP channel responsible for retinal ON bipolar function. , 2010, Cell calcium.

[4]  E. Mauceli,et al.  Fine-mapping and mutation analysis of TRPM1: a candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses. , 2010, Briefings in functional genomics.

[5]  Makoto Nakamura,et al.  TRPM1 mutations are associated with the complete form of congenital stationary night blindness , 2010, Molecular vision.

[6]  M. Tachibana,et al.  TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade , 2009, Proceedings of the National Academy of Sciences of the United States of America.

[7]  T. Léveillard,et al.  TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness. , 2009, American journal of human genetics.

[8]  G. Holder,et al.  Recessive mutations of the gene TRPM1 abrogate ON bipolar cell function and cause complete congenital stationary night blindness in humans. , 2009, American journal of human genetics.

[9]  M. Kamermans,et al.  Mutations in TRPM1 are a common cause of complete congenital stationary night blindness. , 2009, American journal of human genetics.

[10]  R. Duvoisin,et al.  TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells , 2009, Proceedings of the National Academy of Sciences.

[11]  Adam Byron,et al.  Proteomic Analysis of Integrin-Associated Complexes Identifies RCC2 as a Dual Regulator of Rac1 and Arf6 , 2009, Science Signaling.

[12]  D. Clapham,et al.  TRPM1 Forms Ion Channels Associated with Melanin Content in Melanocytes , 2009, Science Signaling.

[13]  R. Bellone,et al.  Differential Gene Expression of TRPM1, the Potential Cause of Congenital Stationary Night Blindness and Coat Spotting Patterns (LP) in the Appaloosa Horse (Equus caballus) , 2008, Genetics.

[14]  S. Archer,et al.  Clinical and electroretinographic characteristics of congenital stationary night blindness in the Appaloosa and the association with the leopard complex. , 2007, Veterinary ophthalmology.

[15]  F. Riemslag,et al.  Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram. , 2005, Investigative ophthalmology & visual science.

[16]  C. Nunnery,et al.  Congenital stationary night blindness in a Thoroughbred and a Paso Fino. , 2005, Veterinary ophthalmology.

[17]  Bernd Nilius,et al.  TRP Channels in Disease , 2005, Science's STKE.

[18]  J. Murray,et al.  Linkage of the grey coat colour locus to microsatellites on horse chromosome 25. , 2002, Animal genetics.

[19]  A. Sober,et al.  Melastatin expression and prognosis in cutaneous malignant melanoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  S. Jacobson,et al.  Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness , 2000, Nature Genetics.

[21]  H. Lester,et al.  Genetic Inactivation of an Inwardly Rectifying Potassium Channel (Kir4.1 Subunit) in Mice: Phenotypic Impact in Retina , 2000, The Journal of Neuroscience.

[22]  S. Nawy.  Regulation of the On Bipolar Cell mGluR6 Pathway by Ca2+ , 2000, The Journal of Neuroscience.

[23]  N. Vardi.  Alpha subunit of Go localizes in the dendritic tips of ON bipolar cells , 1998, The Journal of comparative neurology.

[24]  P. Robinson,et al.  Functional Coupling of a Human Retinal Metabotropic Glutamate Receptor (hmGluR6) to Bovine Rod Transducin and Rat Go in an in Vitro Reconstitution System* , 1997, The Journal of Biological Chemistry.

[25]  E. Smith,et al.  Congenital stationary night blindness: an animal model. , 1978, Investigative ophthalmology & visual science.

[26]  G. Schubert,et al.  Beitrag zur Analyse des menschlichen Elektroretinogramms , 1952 .