Redundant contribution of a Transient Receptor Potential cation channel Member 1 exon 11 single nucleotide polymorphism to equine congenital stationary night blindness
| Autor: | Emily E. John, George W. Forsyth, John C. H. Ching, Bruce H. Grahn, Michelle Lynn Scott, Lynne S. Sandmeyer, Rebecca R. Bellone, Matthew E. Loewen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Eye Diseases Primary transcript Exon 0302 clinical medicine Transcription (biology) Night Blindness Myopia Congenital stationary night blindness Cells Cultured Genetics Cultured RNA-Binding Proteins Eye Diseases Hereditary Genetic Diseases X-Linked General Medicine Single Nucleotide Exons Hereditary Genetic Diseases RNA splicing Research Article Cells TRPM Cation Channels Nerve Tissue Proteins Biology Appaloosa Polymorphism Single Nucleotide Microbiology 03 medical and health sciences Neuro-Oncological Ventral Antigen Animals Horses Veterinary Sciences Polymorphism Gene Eye Disease and Disorders of Vision TRPM1 Messenger RNA Binding Sites General Veterinary Intron Neurosciences X-Linked veterinary(all) Molecular biology 030104 developmental biology Transient Receptor Potential cation channel Member 1 RNA Horse Diseases Biochemistry and Cell Biology 030217 neurology & neurosurgery |
| Zdroj: | BMC veterinary research, vol 12, iss 1 BMC Veterinary Research |
| Popis: | BackgroundCongenital stationary night-blindness (CSNB) is a recessive autosomal defect in low-light vision in Appaloosa and other horse breeds. This condition has been mapped by linkage analysis to a gene coding for the Transient Receptor Potential cation channel Member 1 (TRPM1). TRPM1 is normally expressed in the ON-bipolar cells of the inner nuclear layer of the retina. Down-regulation of TRPM1 expression in CSNB results from a transposon-like insertion in intron 1 of the TRPM1 gene. Stop transcription signals in this transposon significantly reduce TRPM1 primary transcript levels in CSNB horses. This study describes additional contributions by a second mutation of the TRPM1 gene, the ECA1 108,249,293 C > T SNP, to down-regulation of transcription of the TRPM1 gene in night-blind horses. This TRPM1 SNP introduces a consensus binding site for neuro-oncological ventral antigen 1 (Nova-1) protein in the primary transcript. Nova-1 binding disrupts normal splicing signals, producing unstable, non-functional mRNA transcripts.ResultsRetinal bipolar cells express both TRPM1 and Nova-1 proteins. In vitro addition of Nova-1 protein retards electrophoretic migration of TRPM1 RNA containing the ECA1 108,249,293 C > T SNP. Up-regulating Nova-1 expression in primary cultures of choroidal melanocytes carrying the intron 11 SNP caused an average log 2-fold reduction of ~6 (64-fold) of TRPM1 mRNA expression.ConclusionsThese finding suggest that the equine TRPM1 SNP can act independently to reduce survival of TRPM1 mRNA escaping the intron 1 transcriptional stop signals in CSNB horses. Coexistence and co-inheritance of two independent TRPM1 mutations across 1000 equine generations suggests a selective advantage for the apparently deleterious CSNB trait. |
| Databáze: | OpenAIRE |
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