Vogler C, Homan S, Pung A, Thorpe C, Barker J, Birkenmeier E H, Upadhya P
Department of Pathology, Saint Louis University School of Medicine, Missouri 63104, USA.
J Am Soc Nephrol. 1999 Dec;10(12):2534-9. doi: 10.1681/ASN.V10122534.
Patients with inherited cystic kidney diseases have progressive cystic dilation of nephrons with concomitant loss of functional renal parenchyma and renal failure. Animal models of inherited cystic kidney disease are useful for study of the pathogenesis and molecular basis of cystic renal diseases. This article describes the clinical and pathologic features in two spontaneously occurring murine models of inherited polycystic kidney disease due to independent allelic mutations on mouse chromosome 8. The mutations, designated kat and kat2J, affect a chromosomal segment homologous to a region of human chromosome 4q35; the altered gene has not yet been identified. An allelism test showed that the mutations are at the same locus. The phenotype, inherited as an autosomal recessive, is more severe in kat2J/kat2J mice. Their kidneys are morphologically normal at birth, but by 3 mo of age, cysts affect all levels of the nephron. Adult males have testicular hypoplasia and they are sterile. A few of the oldest kat2J/kat2J mice have focal portal bile duct proliferation and dilation. kat2J/kat2J mice develop anemia and uremia and die before 1 yr of age. In kat/kat mice, the renal cystic disease progresses more slowly but is morphologically similar to that of kat2J/kat2J mice. The progressive cystic transformation of the kidneys in these allelic murine models resembles that seen in humans with autosomal dominant polycystic kidney disease.
患有遗传性囊性肾病的患者会出现肾单位进行性囊性扩张，同时功能性肾实质丧失并导致肾衰竭。遗传性囊性肾病的动物模型有助于研究囊性肾病的发病机制和分子基础。本文描述了两种由于小鼠8号染色体上独立的等位基因突变而自发产生的遗传性多囊肾病小鼠模型的临床和病理特征。这些突变被命名为kat和kat2J，影响与人类4号染色体4q35区域同源的一个染色体片段；目前尚未鉴定出发生改变的基因。等位性测试表明这些突变位于同一基因座。该表型以常染色体隐性方式遗传，在kat2J/kat2J小鼠中更为严重。它们的肾脏在出生时形态正常，但到3月龄时，囊肿影响肾单位的各个水平。成年雄性小鼠有睾丸发育不全且不育。一些年龄最大的kat2J/kat2J小鼠有局灶性门静脉胆管增生和扩张。kat2J/kat2J小鼠会出现贫血和尿毒症，并在1岁前死亡。在kat/kat小鼠中，肾囊性疾病进展较慢，但在形态上与kat2J/kat2J小鼠相似。这些等位基因小鼠模型中肾脏的进行性囊性转变类似于人类常染色体显性多囊肾病的情况。
