Abstract. 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, designatedkatandkat2J, 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 inkat2J/kat2Jmice. 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 oldestkat2J/kat2Jmice have focal portal bile duct proliferation and dilation.kat2J/kat2Jmice develop anemia and uremia and die before 1 yr of age. Inkat/katmice, the renal cystic disease progresses more slowly but is morphologically similar to that ofkat2J/kat2Jmice. The progressive cystic transformation of the kidneys in these allelic murine models resembles that seen in humans with autosomal dominant polycystic kidney disease.
Clinical and Pathologic Findings in Two New Allelic Murine Models of Polycystic Kidney Disease