Complex Phenotype of Mice Lacking Occludin, a Component of Tight Junction Strands

TLDR

Occludin is a transmembrane protein localized exclusively to tight junction strands. The study generated and analyzed occludin‑null mice to investigate occludin function. Occludin‑null mice displayed normal birth but postnatal growth retardation, male infertility, abnormal maternal behavior, and widespread histological defects—including gastric inflammation, brain calcification, testicular atrophy, salivary gland alterations, and bone thinning—despite intact tight junction morphology and intestinal barrier function, indicating a more complex role for occludin.

Abstract

Occludin is an integral membrane protein with four transmembrane domains that is exclusively localized at tight junction (TJ) strands. Here, we describe the generation and analysis of mice carrying a null mutation in the occludin gene. Occludin −/− mice were born with no gross phenotype in the expected Mendelian ratios, but they showed significant postnatal growth retardation. Occludin −/− males produced no litters with wild-type females, whereas occludin −/− females produced litters normally when mated with wild-type males but did not suckle them. In occludin −/− mice, TJs themselves did not appear to be affected morphologically, and the barrier function of intestinal epithelium was normal as far as examined electrophysiologically. However, histological abnormalities were found in several tissues, i.e., chronic inflammation and hyperplasia of the gastric epithelium, calcification in the brain, testicular atrophy, loss of cytoplasmic granules in striated duct cells of the salivary gland, and thinning of the compact bone. These phenotypes suggested that the functions of TJs as well as occludin are more complex than previously supposed.