CYSTINURIA IN NEWFOUNDLAND DOGS

纽芬兰犬的胱氨酸尿症

• 批准号: 7391951
• 负责人: PAULA S HENTHORN
• 金额: $ 1.01万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7391951
• 关键词: CYSTINURIA; NEWFOUNDLAND; DOGS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cystinuria is an inherited renal disease characterized by defective amino acid reabsorption and by the formation of cystine uroliths. Different forms of the disease, designated type I and non-type I, can be distinguished clinically and biochemically, and have been associated in cystinuric humans with mutations in the SLC3A1 (rBAT) and SLC7A9 genes, respectively. Cystinuria is primarily inherited as an autosomal recessive trait in humans and the type I form of the disease is most common. Cystinuria has been recognized in many breeds of dogs and a severe form, resembling type I cystinuria, has been characterized in the Newfoundland breed. Breeding studies (supported by this grant) previously demonstrated autosomal recessive inheritance of cystinuria in the Newfoundland dog, suggesting SLC3A1 as a candidate gene for the disease. We cloned and sequenced the canine SLC3A1 cDNA and gene from normal and affected Newfoundland dogs and identified a nonsense mutation in exon 2 of the gene in the cystinuric dogs. This discovery confirms the Newfoundland disease as a true homologue of human type I cystinuria. The knowledge of the gene mutation in the canine model provides the opportunity to use a large animal model to investigate molecular approaches for the treatment of cystinuria and other renal tubular diseases. Studies are also ongoing to investigate cystinuria in the Maned Wolf, a threatened South American canid species with an extremely high incidence of cystinuria. We have analyzed urine samples from many captive animals in the United States in order to determine the mode of inheritance and characterize the type of cystinuria. These studies are ongoing and funded in part by the Morris Animal Foundation.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。胱氨酸尿症是一种遗传性肾脏疾病，其特征是氨基酸重吸收缺陷和胱氨酸尿石的形成。该疾病的不同形式（称为 I 型和非 I 型）可以通过临床和生化来区分，并且在患有胱氨酸尿症的人中分别与 SLC3A1 (rBAT) 和 SLC7A9 基因突变相关。胱氨酸尿症主要作为人类常染色体隐性遗传，I 型疾病最为常见。胱氨酸尿症已在许多品种的狗中被发现，并且在纽芬兰品种中已发现严重的形式，类似于 I 型胱氨酸尿症。育种研究（由此项资助支持）先前证明纽芬兰犬的胱氨酸尿症是常染色体隐性遗传，表明 SLC3A1 是该疾病的候选基因。我们对正常和受影响的纽芬兰犬的犬 SLC3A1 cDNA 和基因进行了克隆和测序，并在胱氨酸尿犬的基因外显子 2 中发现了无义突变。这一发现证实纽芬兰病是人类 I 型胱氨酸尿症的真正同源物。对犬模型中基因突变的了解为使用大型动物模型研究治疗胱氨酸尿症和其他肾小管疾病的分子方法提供了机会。鬃狼的胱氨酸尿症研究也在进行中，鬃狼是一种受威胁的南美犬科动物，胱氨酸尿症的发病率极高。我们分析了美国许多圈养动物的尿液样本，以确定遗传模式并表征胱氨酸尿症的类型。这些研究正在进行中，部分由莫里斯动物基金会资助。