Coasy, Tfrc, Drd1 and Drd2 primer sequences.

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive movement and vision disorder in the neurodegeneration with brain iron accumulation family of diseases. PKAN is caused by mutations in PANK2, encoding pantothenate kinase 2, causing an inborn error of coenzyme A metabolism and leading to iron accumulation in the basal ganglia. Peripheral pigmentary retinopathy is common in people with PKAN. The knockout murine model of the orthologous Pank2 gene is known to manifest retinal degeneration through electroretinography, pupillary response and histology analyses. Our longitudinal characterization of the retinopathy in this model reveals reduced visual performance and reduced photoreceptor thickness compared to wild-type mice. Additionally, retinal perturbations in coenzyme A metabolism and dopamine metabolism pathways mimic those previously observed in the brain. These data extend the murine ocular phenotype associated with loss of function of Pank2. With a measurable behavioral, structural and mechanistic retinal phenotype, this mouse model is an ideal pre-clinical model that can be used to evaluate therapeutics for PKAN.

泛酸激酶相关神经变性病（Pantothenate kinase-associated neurodegeneration, PKAN）是隶属于脑铁沉积性神经变性病家族的常染色体隐性遗传运动与视觉障碍性疾病。PKAN由PANK2基因突变所致，该基因编码泛酸激酶2（pantothenate kinase 2），会引发辅酶A代谢先天性代谢异常，并导致基底神经节出现铁沉积。PKAN患者常并发周边色素性视网膜病变（peripheral pigmentary retinopathy）。现有研究表明，靶向同源Pank2基因的敲除小鼠模型可通过视网膜电图（electroretinography）、瞳孔反应及组织学分析观测到视网膜变性表型。本研究对该模型的视网膜病变开展纵向表征后发现，与野生型小鼠（wild-type mice）相比，其视觉功能下降且感光细胞厚度降低。此外，该模型中辅酶A代谢与多巴胺代谢通路的视网膜扰动特征，与此前在脑部观测到的表型高度相似。上述数据拓展了Pank2功能缺失相关的小鼠眼部表型谱。鉴于该小鼠模型具备可量化的行为学、结构学及机制性视网膜表型，其是评估PKAN治疗药物的理想临床前模型（pre-clinical model）。