Establishment of a novel rat model for cystinosis

胱氨酸病是一种罕见的溶酶体积存疾病，其特征是半胱氨酸在各器官的异常积聚。所有组织中半胱氨酸的积累最终导致多系统疾病。致病基因CTNS编码胱氨酸，即溶酶体半胱氨酸转运蛋白。我们在LEA大鼠的Ctns基因中发现了一个13 bp的缺失，并在F344遗传背景下建立了一个携带LEA大鼠Ctns突变基因的同源菌株。我们还建立了一种快速测定半胱氨酸的高效液相色谱法，以评估其在细胞和组织中的积累。缺乏Ctns功能的基因大鼠有望成为了解胱氨酸病的有益模型动物。

Cystinosis is a rare lysosomal storage disease characterized by the abnormal accumulation of cysteine in various organs. Accumulation of cysteine in all tissues eventually leads to multisystemic disease. The causative gene, CTNS, encodes cystinosin, the lysosomal cysteine transporter. We identified a 13-bp deletion within Ctns gene in LEA rat, and have established a congenic strain carrying mutant Ctns gene from LEA rat on F344 genetic background. We also developed a simple and rapid method for determination of cysteine using HPLC to evaluate its accumulation in cells and tissues. The congenic rats lacking the function of Ctns is expected to be a useful for model animal of understanding cystinosis.