CD44-deficient mice develop normally with changes in subpopulations and recirculation of lymphocytes subsets

Cell adhesion molecules are considered to be pivotal elements required for proper embryo development. The transmembrane glycoprotein CD44, which is ex pressed in numerous splice variants on the surface of many different cell t ypes and tissues, has been suggested to be involved in several physiologica l processes such as cell-cell interactions, signal transduction, and lympho cyte homing-and trafficking during embryogenesis and in the adult organism. Some splice variants are thought to play an important role in tumor progre ssion. To investigate the physiological roles of CD44 in vivo, we abolished expression of all isoforms of CD44 in mice:by targeted insertion of a lacZ /neo cassette into the reading frame of the leader peptide. CD44-deficient mice are viable without obvious developmental defects and show no overt abn ormalities as adults. However, CD44-deficient lymphocytes exhibit impaired entry into the adult thymus, although lymphocyte development is apparently unaltered. Our data indicate that all splice variants of CD44 are dispensab le for embryonic development and implicate a critical function for CD44 in lymphocyte recirculation.