Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis
Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis
复制标题
DOI：
10.1073/pnas.93.11.5307
复制
发表时间：
1996-05-28
影响因子：
11.1
通讯作者：
Tischfield, JA
中科院分区：
文献类型：
--
作者：
Engle, SJ;Stockelman, MG;Tischfield, JA
腺嘌呤磷酸核糖基转移酶（APRT）缺乏症是一种常染色体隐性遗传综合征，其特征是腺嘌呤和高度不溶性化合物2，8-二羟基腺嘌呤（DHA）的尿排泄，可导致肾结石或肾衰竭。胚胎干细胞中的靶向同源重组用于产生缺乏APRT的小鼠。Aprt等位基因缺失的纯合子小鼠在尿液中分泌腺嘌呤和DHA晶体。肾脏组织病理学显示广泛的肾小管扩张、炎症、坏死和纤维化，不同小鼠背景之间的严重程度不同。因此，这些小鼠的生化和组织学变化模拟了人类疾病，并提供了一个合适的人类遗传性肾结石模型。
Adenine phosphoribosyltransferase (APRT) deficiency in humans is an autosomal recessive syndrome characterized by the urinary excretion of adenine and the highly insoluble compound 2,8-dihydroxyadenine (DHA) that can produce kidney stones or renal failure. Targeted homologous recombination in embryonic stem cells was used to produce mice that lack APRT. Mice homozygous for a null Aprt allele excrete adenine and DHA crystals in the urine. Renal histopathology showed extensive tubular dilation, inflammation, necrosis, and fibrosis that varied in severity between different mouse backgrounds. Thus, biochemical and histological changes in these mice mimic the human disease and provide a suitable model of human hereditary nephrolithiasis.