New form of X-linked dominant hereditary nephritis in dogs.
New form of X-linked dominant hereditary nephritis in dogs.
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DOI：
10.2460/ajvr.1999.60.03.373
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发表时间：
1999-03
影响因子：
1
通讯作者：
G. Lees;Helman Rg;C. Kashtan;A. Michael;L. Homco;N. Millichamp;Camacho Zt;J. Templeton;Y. Ninomiya;Y. Sado;I. Naito;Youngki Kim
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文献类型：
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作者：
G. Lees;Helman Rg;C. Kashtan;A. Michael;L. Homco;N. Millichamp;Camacho Zt;J. Templeton;Y. Ninomiya;Y. Sado;I. Naito;Youngki Kim
目的探讨一种新的遗传性肾炎（HN）的特征。动物父母和16只第一代后代（8只雄性，8只雌性）。程序对发生肾衰竭的青春期犬实施安乐死并进行尸检。对未受影响的狗进行监测，直到它们至少2岁。研究包括从受影响和未受影响的犬中获得的肾脏的光学和电子显微镜检查，以及肾脏和表皮基底膜（BM）中IV型胶原链的免疫标记。在从受影响和未受影响的男性分离的基因组DNA中测定了COL 4A 5基因外显子35的一部分的核苷酸序列。结果8只雄性和8只雌性子代中分别有7只和2只出现蛋白尿和幼年型慢性肾功能衰竭，雄性子代进展更快。α 3-α 6（IV）链的标记在受累雄性动物的肾BM中完全不存在，在受累雌性动物中节段性不存在。受影响犬肾小球BM（GBM）中α 1-α 2（IV）链的表达增加。在受累雄性和受累雌性中，表皮BM中不存在α 5-α 6（IV）链标记。电镜下观察到病犬GBM中HN的特征性改变。在患病犬中，COL 4A 5外显子35的序列是正常的。结论该肾脏疾病是X连锁显性遗传HN的一例，具有典型的GBM超微结构和α（IV）链表达异常。临床相关性和对人类医学的影响：患有这种自然获得性进行性肾病的犬可用于研究人类和犬中类似疾病的发病机制和治疗。
OBJECTIVE To determine features of a new form of hereditary nephritis (HN) in dogs. ANIMALS Parents and 16 first-generation offspring (8 males, 8 females). PROCEDURE Adolescent dogs that developed renal failure were euthanatized and necropsied. Unaffected dogs were monitored until they were at least 2 years old. Studies included light and electron microscopy of kidneys obtained from affected and unaffected dogs and immunolabeling for collagen-IV chains in renal and epidermal basement membranes (BM). The nucleotide sequence of a portion of exon 35 of the COL4A5 gene was determined in genomic DNA isolated from affected and unaffected males. RESULTS 7 of 8 male and 2 of 8 female offspring had proteinuria and juvenile-onset chronic renal failure, which progressed more rapidly in the males. Labeling for alpha3-alpha6(IV) chains was completely absent in renal BM of affected males and segmentally absent in affected females. Expression of alpha1-alpha2(IV) chains in glomerular BM (GBM) of affected dogs was increased. Labeling for alpha5-alpha6(IV) chains in epidermal BM was absent in affected males and segmental in affected females. Ultrastructural changes characteristic of HN were observed in GBM of affected dogs. The sequence of exon 35 of COL4A5 was normal in affected dogs. CONCLUSIONS This renal disease is an example of X-linked dominant HN, with typical abnormalities of GBM ultrastructure and alpha(IV) chain expression. CLINICAL RELEVANCE AND IMPLICATIONS FOR HUMAN MEDICINE: Dogs with this naturally acquired progressive renal disease can be used to investigate the pathogenesis and treatment of similar disorders in human beings and dogs.