Experimental and Molecular Immunology and Neurogenetics (INEM), Orléans University, Centre National de la Recherche Scientifique (CNRS) UMR7355, Orléans, France.
Institute of NeuroPhysiopathology (INP), Aix-Marseille University, CNRS UMR7051, Marseille, France.
Kidney360. 2021 Sep 17;2(11):1793-1806. doi: 10.34067/KID.0001732021. eCollection 2021 Nov 25.
Xanthinuria type II is a rare autosomal purine disorder. This recessive defect of purine metabolism remains an under-recognized disorder.
Mice with targeted disruption of the molybdenum cofactor sulfurase () gene were generated to enable an integrated understanding of purine disorders and evaluate pathophysiologic functions of this gene which is found in a large number of pathways and is known to be associated with autism.
-deficient mice die with 4 weeks of age due to renal failure of distinct obstructive nephropathy with xanthinuria, xanthine deposits, cystic tubular dilation, Tamm-Horsfall (uromodulin) protein (THP) deposits, tubular cell necrosis with neutrophils, and occasionally hydronephrosis with urolithiasis. Obstructive nephropathy is associated with moderate interstitial inflammatory and fibrotic responses, anemia, reduced detoxification systems, and important alterations of the metabolism of purines, amino acids, and phospholipids. Conversely, heterozygous mice expressing reduced MOCOS protein are healthy with no apparent pathology.
-deficient mice develop a lethal obstructive nephropathy associated with profound metabolic changes. Studying MOCOS functions may provide important clues about the underlying pathogenesis of xanthinuria and other diseases requiring early diagnosis.
黄嘌呤尿症 II 型是一种罕见的常染色体嘌呤代谢紊乱。这种嘌呤代谢的隐性缺陷仍然是一种未被充分认识的疾病。
通过靶向敲除钼辅因子硫代酶（）基因的方法，生成了小鼠模型，以便对嘌呤代谢紊乱进行综合理解，并评估该基因的病理生理功能。该基因存在于大量的通路中，已知与自闭症有关。
由于黄嘌呤尿、黄嘌呤沉积、囊性管状扩张、Tamm-Horsfall（尿调蛋白）蛋白（THP）沉积、肾小管细胞坏死伴中性粒细胞浸润，以及偶尔伴有肾积水和尿路结石的特征性梗阻性肾病，-缺陷小鼠在 4 周龄时死亡。梗阻性肾病与中度间质炎症和纤维化反应、贫血、解毒系统减少以及嘌呤、氨基酸和磷脂代谢的重要改变有关。相反，表达减少的 MOCOS 蛋白的杂合子小鼠则健康，没有明显的病理变化。
-缺陷小鼠会发生致命的梗阻性肾病，伴有深刻的代谢变化。研究 MOCOS 的功能可能为黄嘌呤尿症和其他需要早期诊断的疾病的潜在发病机制提供重要线索。
