Newton J M, Orlow S J, Barsh G S
Department of Pediatrics, Stanford University School of Medicine, California 94305-5428, USA.
Genomics. 1996 Oct 15;37(2):219-25. doi: 10.1006/geno.1996.0545.
Ocular albinism type 1 (OA1) is an X-linked human genetic disorder that affects retinal pigment cells and, to a lesser degree, neural crest-derived melanocytes. The OA1 gene is located close to the pseudoautosomal region and predicts a novel protein whose function is unknown. However, histologic studies of affected patients have suggested a potential role in melanosome biogenesis. Here we report the isolation and characterization of the mouse homolog of the human OA1 gene, termed Moa1. Two Moa1 isoforms were isolated from a melanoma cDNA library and predicted to encode proteins of 405 and 249 amino acids with six and two transmembrane-spanning regions, respectively. Interspecific backcross mapping yielded a map order and distances (cM) of cen-Moa1-3.1 +/- 1.8-Piga-2.1 +/- 1.5-Amel, indicating that Moa1 is located much farther away from the pseudoautosomal region than its human homolog. In adult tissues, both Moa1 isoforms were detected in the eye by Northern hybridization. In neonatal tissues, Moa1 RNA was detected in both skin and eyes by Northern hybridization and was not affected by the absence of pigment in mice carrying the albino mutation, or by the type of pigment synthesized, i.e., eumelanin vs pheomelanin, in mice carrying the black-and-tan mutation. Expression of Moa1 RNA was not detected in embryonic tissues by Northern analysis or by in situ hybridization despite the active synthesis of ocular pigment by E16.5. These results provide insight into the structure and possible function of the OA1 protein and suggest a more complex relationship between the human and mouse X chromosomes than was previously thought to exist.
1型眼白化病（OA1）是一种X连锁的人类遗传疾病，会影响视网膜色素细胞，在较小程度上也会影响神经嵴衍生的黑素细胞。OA1基因位于假常染色体区域附近，预测会编码一种功能未知的新型蛋白质。然而，对受影响患者的组织学研究表明其在黑素小体生物发生中可能发挥作用。在此，我们报告了人类OA1基因的小鼠同源物（称为Moa1）的分离和表征。从黑色素瘤cDNA文库中分离出两种Moa1异构体，预计分别编码405和249个氨基酸的蛋白质，分别具有六个和两个跨膜区域。种间回交图谱分析得出的图谱顺序和距离（厘摩）为cen-Moa1-3.1 +/- 1.8-Piga-2.1 +/- 1.5-Amel，这表明Moa1比其人类同源物距离假常染色体区域更远。在成年组织中，通过Northern杂交在眼睛中检测到了两种Moa1异构体。在新生组织中，通过Northern杂交在皮肤和眼睛中均检测到了Moa1 RNA，并且在携带白化病突变的小鼠中，其不受色素缺失的影响，在携带黑褐毛色突变的小鼠中，也不受合成色素类型（即真黑素与褐黑素）的影响。尽管在胚胎期16.5天眼部色素在活跃合成，但通过Northern分析或原位杂交在胚胎组织中均未检测到Moa1 RNA的表达。这些结果为OA1蛋白的结构和可能功能提供了深入了解，并表明人类和小鼠X染色体之间的关系比以前认为的更为复杂。
