Complex phenotype of mice lacking occludin, a component of tight junction strands

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