Department of Medical Genetics, University of Wisconsin, Madison, WI 53706, USA.
Genetics. 2010 Dec;186(4):1337-44. doi: 10.1534/genetics.110.120840. Epub 2010 Sep 27.
X-linked retinoschisis (XLRS) is a form of macular degeneration with a juvenile onset. This disease is caused by mutations in the retinoschisin (RS1) gene. The major clinical pathologies of this disease include splitting of the retina (schisis) and a loss in synaptic transmission. Human XLRS patients display a broad range in phenotypic severity, even among family members with the same mutation. This variation suggests the existence of genetic modifiers that may contribute to disease severity. Previously, we reported the identification of a modifier locus, named Mor1, which affects severity of schisis in a mouse model of XLRS (the Rs1tmgc1 mouse). Homozygosity for the protective AKR allele of Mor1 restores cell adhesion in Rs1tmgc1 mice. Here, we report our study to identify the Mor1 gene. Through collecting recombinant mice followed by progeny testing, we have localized Mor1 to a 4.4-Mb region on chromosome 7. In this genetic region, the AKR strain is known to carry a mutation in the tyrosinase (Tyr) gene. We observed that the schisis phenotype caused by the Rs1 mutation is rescued by a Tyr mutation in the C57BL/6J genetic background, strongly suggesting that Tyr is the Mor1 gene.
X 连锁性视网膜炎劈裂症（XLRS）是一种少年发病的黄斑变性。这种疾病是由视网膜劈裂蛋白（RS1）基因突变引起的。这种疾病的主要临床病理学特征包括视网膜劈裂（劈裂症）和突触传递丧失。人类 XLRS 患者的表型严重程度差异很大，即使是具有相同突变的家庭成员也是如此。这种变异表明存在遗传修饰因子，可能会影响疾病的严重程度。此前，我们报道了一个修饰基因座 Mor1 的鉴定，该基因座影响 XLRS 小鼠模型（Rs1tmgc1 小鼠）中劈裂症的严重程度。Mor1 的保护性 AKR 等位基因的纯合性可恢复 Rs1tmgc1 小鼠中的细胞黏附。在这里，我们报告了我们确定 Mor1 基因的研究。通过收集重组小鼠并进行后代测试，我们将 Mor1 定位到 7 号染色体上的 4.4-Mb 区域。在这个遗传区域中，AKR 品系已知在酪氨酸酶（Tyr）基因中存在突变。我们观察到，在 C57BL/6J 遗传背景下，Rs1 突变引起的劈裂表型可被 Tyr 突变挽救，强烈表明 Tyr 就是 Mor1 基因。
