Bellone Rebecca R, Brooks Samantha A, Sandmeyer Lynne, Murphy Barbara A, Forsyth George, Archer Sheila, Bailey Ernest, Grahn Bruce
Department of Biology, University of Tampa, Tampa, FL 33606, USA.
Genetics. 2008 Aug;179(4):1861-70. doi: 10.1534/genetics.108.088807. Epub 2008 Jul 27.
The appaloosa coat spotting pattern in horses is caused by a single incomplete dominant gene (LP). Homozygosity for LP (LP/LP) is directly associated with congenital stationary night blindness (CSNB) in Appaloosa horses. LP maps to a 6-cM region on ECA1. We investigated the relative expression of two functional candidate genes located in this LP candidate region (TRPM1 and OCA2), as well as three other linked loci (TJP1, MTMR10, and OTUD7A) by quantitative real-time RT-PCR. No large differences were found for expression levels of TJP1, MTMR10, OTUD7A, and OCA2. However, TRPM1 (Transient Receptor Potential Cation Channel, Subfamily M, Member 1) expression in the retina of homozygous appaloosa horses was 0.05% the level found in non-appaloosa horses (R = 0.0005). This constitutes a >1800-fold change (FC) decrease in TRPM1 gene expression in the retina (FC = -1870.637, P = 0.001) of CSNB-affected (LP/LP) horses. TRPM1 was also downregulated in LP/LP pigmented skin (R = 0.005, FC = -193.963, P = 0.001) and in LP/LP unpigmented skin (R = 0.003, FC = -288.686, P = 0.001) and was downregulated to a lesser extent in LP/lp unpigmented skin (R = 0.027, FC = -36.583, P = 0.001). TRP proteins are thought to have a role in controlling intracellular Ca(2+) concentration. Decreased expression of TRPM1 in the eye and the skin may alter bipolar cell signaling as well as melanocyte function, thus causing both CSNB and LP in horses.
马的阿帕卢萨毛色斑点模式是由单个不完全显性基因（LP）引起的。LP的纯合性（LP/LP）与阿帕卢萨马的先天性静止性夜盲症（CSNB）直接相关。LP定位于ECA1上一个6厘摩的区域。我们通过定量实时逆转录PCR研究了位于该LP候选区域的两个功能候选基因（TRPM1和OCA2）以及其他三个连锁位点（TJP1、MTMR10和OTUD7A）的相对表达。在TJP1、MTMR10、OTUD7A和OCA2的表达水平上未发现大的差异。然而，纯合阿帕卢萨马视网膜中TRPM1（瞬时受体电位阳离子通道，M亚家族，成员1）的表达仅为非阿帕卢萨马的0.05%（R = 0.0005）。这构成了受CSNB影响（LP/LP）马视网膜中TRPM1基因表达>1800倍的变化（FC）降低（FC = -1870.637，P = 0.001）。TRPM1在LP/LP有色皮肤（R = 0.005，FC = -193.963，P = 0.001）和LP/LP无色皮肤（R = 0.003，FC = -288.686，P = 0.001）中也下调，在LP/lp无色皮肤中下调程度较小（R = 0.027，FC = -36.583，P = 0.001）。TRP蛋白被认为在控制细胞内Ca(2+)浓度中起作用。TRPM1在眼睛和皮肤中的表达降低可能会改变双极细胞信号传导以及黑素细胞功能，从而导致马出现CSNB和LP。
