Current advances in molecular genetics of autosomal-dominant polycystic kidney disease
Current advances in molecular genetics of autosomal-dominant polycystic kidney disease
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常染色体显性多囊肾病分子遗传学研究进展
DOI：
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发表时间：
2001
影响因子：
3.2
通讯作者：
Guan
中科院分区：
文献类型：
--
作者：
Guan
常染色体显性多囊肾病由至少两个致病基因PKD 1和PKD 2引起。人类患者和靶向Pkd 1和Pkd 2突变小鼠模型中相同的临床表型提供了两种基因产物在相同致病途径中起作用的证据。PKD 1和PKD 2直接相互作用的发现意味着两种基因产物多囊蛋白-1和多囊蛋白-2在同一分子复合物中发挥功能作用。这两个基因的种系突变谱和从个体PKD 1或PKD 2囊肿中鉴定的体细胞突变表明PKD 1或PKD 2功能的丧失是常染色体显性多囊肾病中囊肿形成的机制。一种新的小鼠模型Pkd 2 WS 25/−已经证明杂合性丢失是常染色体显性多囊肾病的分子机制。最近，对PKD 1和PKD 2在人类或小鼠中的表达模式的研究表明，多囊蛋白1和多囊蛋白2似乎有其各自的功能作用，即使这些多囊蛋白的大部分功能在人类和小鼠发育过程中是平行的。Pkd 2缺陷小鼠具有心脏间隔缺陷，但Pkd 1敲除小鼠不具有这种表型。另一方面，与Pkd 1相比，Pkd 2在中枢神经系统中的表达水平非常低。此外，在间充质凝聚过程中，Pkd 1的表达水平增加，而Pkd 2的表达没有变化。初步数据显示，PKD 1/PKD 2复合反式杂合子在肾脏中具有比年龄匹配的1型或2型常染色体显性多囊肾病的杂合子更严重的囊性表型。这一发现表明，PKD 1可能是PKD 2疾病严重程度的修饰因子，反之亦然。连续PKD 1/TSC 2综合征表型的特征和来自Krd小鼠的数据暗示TSC 2和PAX 2也可能作为常染色体显性多囊肾病疾病严重程度的潜在修饰剂。
Autosomal-dominant polycystic kidney disease results from at least two causal genes, PKD1 and PKD2. The identical clinical phenotype in human patients and targeted Pkd1 and Pkd2 mutant mouse models provides evidence that both gene products act in the same pathogenic pathway. The discovery of direct PKD1 and PKD2 interactions implies that both gene products, polycystin-1 and polycystin-2, play a functional role in the same molecular complex. The spectrum of germ-line mutations in both genes and the somatic mutations identified from individual PKD1 or PKD2 cysts indicate that loss of function of either PKD1 or PKD2 is the mechanism of cystogenesis in autosomal-dominant polycystic kidney disease. A novel mouse model, Pkd2WS25/−, has proved that loss of heterozygosity is the molecular mechanism of autosomal-dominant polycystic kidney disease. Recently, studies on the expression patterns of PKD1 and PKD2 in humans or mice indicate that polycystin 1 and polycystin 2 seem to have their own respective functional roles, even though most of the functions of these polycystins are parallel during human and mouse development. Pkd2-deficient mice have cardiac septum defects, but Pkd1 knockout mice do not have this phenotype. On the other hand, Pkd2 has a very low level of expression in the central nervous system when compared with Pkd1. In addition, the level of expression of Pkd1 is increased during mesenchymal condensation, whereas Pkd2 expression is unchanged. Preliminary data have shown that the PKD1/PKD2 compound trans-heterozygous has a more severe cystic phenotype in the kidney than that of an age-matched heterozygous type 1 or type 2 of autosomal-dominant polycystic kidney disease alone. This finding suggests that PKD1 may be a modifier of disease severity for PKD2, and vice versa. The characteristics of the contiguous PKD1/TSC2 syndrome phenotypes and the data from Krd mice imply that TSC2 and PAX2 may also serve as potential modifiers for the disease severity of autosomal-dominant polycystic kidney disease.
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影响因子：
4.4
作者：
G. Wu;T. Mochizuki;T. C. Le;Y. Cai;T. Hayashi;D. Reynolds;S. Somlo
通讯作者：
G. Wu;T. Mochizuki;T. C. Le;Y. Cai;T. Hayashi;D. Reynolds;S. Somlo
DOI：
10.1152/ajprenal.1997.272.4.f451
发表时间：
1997-04-01
影响因子：
4.2
作者：
Geng, L;Segal, Y;Zhou, J
通讯作者：
Zhou, J
常染色体显性多囊肾病患者卵巢囊肿的发生频率。
DOI：
10.1016/s0272-6386(99)70117-4
发表时间：
1999
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Stamm,ER;Townsend,RR;Johnson,AM;Garg,K;Manco-Johnson,M;Gabow,PA
通讯作者：
Gabow,PA
DOI：
10.1073/pnas.97.8.4017
发表时间：
2000-04-11
影响因子：
11.1
作者：
Gallagher, AR;Cedzich, A;Witzgall, R
通讯作者：
Witzgall, R
影响因子：
9.8
作者：
Watnick, T;Phakdeekitcharoen, B;Germino, GG
通讯作者：
Germino, GG