Clinical and pathologic findings in two new allelic murine models of polycystic kidney disease

Patients with inherited cystic kidney diseases have progressive cystic dila tion of nephrons with concomitant loss of functional renal parenchyma and r enal failure. Animal models of inherited cystic kidney disease are useful f or study of the pathogenesis and molecular basis of cystic renal diseases. This article describes the clinical and pathologic features in two spontane ously occurring murine models of inherited polycystic kidney disease due to independent allelic mutations on mouse chromosome 8. The mutations, design ated kat and kat(2J), affect a chromosomal segment homologous to a region o f human chromosome 4q35; the altered gene has not yet been identified. An a llelism test showed that the mutations are at the same locus. The phenotype , inherited as an autosomal recessive, is more severe in kat(2J)/kat(2J) mi ce. Their kidneys are morphologically normal at birth, but by 3 mo of age, cysts affect all Levels of the nephron. Adult males have testicular hypopla sia and they are sterile. A few of the oldest kat(2J)/kat(2J) mice have foc al portal bile duct proliferation and dilation, kat(2J)/kat(2J) mice develo p 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 tha t of kat(2J)/kat(2J) mice. The progressive cystic transformation of the kid neys in these allelic murine models resembles that seen in humans with auto somal dominant polycystic kidney disease.